SNPMiner Trials by Shray Alag

L858R (332) T790M (322) V600E (266) T315I (107) L861Q (92) M184V (68) V617F (58) K65R (53) G20210A (53) V600K (52) C282Y (50) V66M (49) G551D (42) P13K (39) C677T (35) A118G (29) I84V (27) V158M (26) H63D (25) V32I (24) S768I (24) I50V (23) I47V (21) K103N (21) K27M (20) Y181C (20) L33F (19) T380A (18) L76V (18) G12C (18) D842V (18) R117H (17) D816V (17) S1251N (17) S1255P (17) G178R (17) G1244E (17) S549R (17) G1349D (17) V82A (16) M41L (16) S549N (16) C3435T (16) G551S (16) Q151M (16) Q12H (15) K219Q (15) I54L (15) K70E (14) C797S (14) G719A (13) L90M (13) L74V (13) E138A (13) D67N (13) K70R (13) L89V (13) L210W (13) Y188L (13) G11778A (12) P4503A (12) L265P (12) M46I (12) I54M (12) G12D (12) E255K (12) V11I (12) R132H (12) G48V (11) V299L (11) D961H (11) T74P (11) R192G (11) T25W (10) K101E (10) G2677T (9) V106A (9) G12V (9) M184I (9) H221Y (9) V30M (9) Y253H (9) V600D (9) G1691A (8) F317L (8) F227C (8) T215Y (8) I50L (8) A1298C (8) L100I (8) I148M (7) N155H (7) F359C (7) S298P (7) G190A (7) M230I (7) C1236T (7) V600R (7) Y188C (7) G2019S (7) Q12W (6) P225H (6) Y93H (6) V108I (6) A3243G (6) G93A (6) G73S (6) P12A (6) Y115F (6) E545K (6) Q148H (6) Y537S (6) E542K (6) I10A (6) M230L (6) H1047R (6) N40D (6) D299G (6) N236T (6) D30N (6) M235T (6) T315A (6) D538G (6) T87Q (5) I47A (5) L74I (5) E92Q (5) N680S (5) A455E (5) M204V (5) D1152H (5) L755S (5) G13D (5) G190S (5) N363S (5) A181V (5) V179L (5) L24I (5) N88S (5) A2143G (5) T399I (5) M36I (5) F53L (5) R263K (5) R132C (5) V777L (5) T1405N (4) D579G (4) G719C (4) N370S (4) R117C (4) Q16W (4) L98H (4) A98G (4) K20M (4) E138G (4) E138K (4) L31M (4) E157Q (4) L10F (4) Q80K (4) C31G (4) G1202R (4) Q252H (4) L206W (4) P140K (4) C19P (4) I54V (4) K76T (4) Y537C (4) I1314L (4) S945L (4) Y402H (4) P1446A (4) V179D (4) N88D (4) A6986G (4) A1166C (4) G970R (4) Y181I (4) R352Q (4) G2385R (4) S310F (4) P67L (4) R1070W (4) G140A (4) E23K (4) S463P (4) T14484C (3) G719S (3) R206H (3) S1400A (3) S1400I (3) A71V (3) C134W (3) R24W (3) C481S (3) T24H (3) V122I (3) T47D (3) A636P (3) S977F (3) G118R (3) G3460A (3) N312S (3) D988Y (3) L444P (3) V659E (3) V769L (3) A147T (3) E10A (3) Q24W (3) L861R (3) R678Q (3) Q27E (3) E17K (3) Q148R (3) A1555G (3) S49G (3) Y537N (3) R16G (3) I10E (3) V158F (3) G21210A (3) K55R (3) V205C (3) Y181V (3) A2142G (3) R506Q (3) E298D (3) L211A (3) R172K (3) V843I (3) Y143R (3) R572Y (3) G143E (3) G1321A (3) V842I (3) H295R (3) G140S (3) T60A (3) P23H (3) F11N (2) S1009A (2) H275Y (2) T733I (2) F1074L (2) I1307K (2) Q36W (2) G250E (2) S77Y (2) E28A (2) E28C (2) E28D (2) T66A (2) S1400C (2) S1400E (2) S1400D (2) L833F (2) D1790G (2) S1400G (2) S1400F (2) R334W (2) L8585R (2) I105V (2) N375S (2) V560G (2) A194T (2) T20S (2) T69D (2) T69S (2) Y93C (2) E138R (2) E138Q (2) F359V (2) R776H (2) Q422H (2) D110H (2) D110E (2) R753Q (2) R404C (2) C283Y (2) L31F (2) S252W (2) L460D (2) L33I (2) R140W (2) R140L (2) R140Q (2) V106I (2) V106M (2) E709K (2) V697L (2) P50I (2) P535H (2) P51S (2) G1314A (2) S492R (2) G308A (2) V191T (2) G71R (2) T215F (2) E56K (2) A2063G (2) D769H (2) L248V (2) E280A (2) Q21D (2) E504K (2) Q141K (2) R496H (2) S100P (2) T128N (2) L536R (2) L536Q (2) L536P (2) A143T (2) T97A (2) G3556C (2) K751Q (2) T4396G (2) V151L (2) G170R (2) A581G (2) L536H (2) G12R (2) L180M (2) W153Q (2) G193E (2) V173L (2) F876L (2) R479H (2) L82M (2) Q28D (2) G190E (2) R347H (2) K601E (2) G16R (2) R831C (2) G5271C (2) V75I (2) G681A (2) A270S (2) L63P (2) L869R (2) P236L (2) R831H (2) T13D (2) H1047L (2) C3670T (2) V34L (2) E255V (2) G469A (2) V57I (2) L144F (2) M233I (2) C825T (2) C8092A (2) G776C (2) G776V (2) F121Y (2) R172S (2) R172W (2) R172M (2) Q192R (2) R172G (2) E380Q (2) F166L (2) A200V (2) Y121F (2) G145R (2) K101P (2) R61C (2) V600M (2) F31I (2) K540E (2) K103H (2) R132V (2) D1270N (2) R1628P (2) R132S (2) V534E (2) R132G (2) R132L (2) V207I (2) K238N (2) G4655A (2) S112A (2) I169T (2) I84A (2) Y129S (1) G1388A (1) S77F (1) R20A (1) V140A (1) C686A (1) I1768V (1) E25K (1) K652E (1) C420R (1) S9304A (1) R337H (1) C421A (1) V189I (1) K304E (1) A7445G (1) D19H (1) L304P (1) Y454S (1) A133S (1) M9T (1) P596L (1) E318D (1) C1156Y (1) N171K (1) A7445C (1) V82F (1) G47A (1) R447H (1) G47E (1) V82L (1) R776C (1) A92T (1) E27Q (1) F1052V (1) P27A (1) A289T (1) L523S (1) H54Y (1) T1095C (1) S428F (1) R400C (1) D313Y (1) Q12M (1) R139C (1) A393T (1) W719R (1) T862I (1) T66K (1) T66I (1) G49A (1) R48G (1) H58C (1) D203E (1) I104F (1) K656E (1) T40S (1) D312N (1) L747P (1) G276T (1) L747S (1) R200W (1) I1171N (1) Q14D (1) S1400K (1) R115G (1) F17L (1) A71T (1) S339F (1) A71L (1) I431V (1) F317V (1) F317S (1) G20201A (1) F317C (1) G2545R (1) C377T (1) P243R (1) S9346A (1) R25L (1) L528M (1) Q222R (1) I22M (1) I107M (1) C1858T (1) L859R (1) G2032R (1) A859S (1) G389D (1) V148I (1) K65E (1) V148G (1) C242T (1) G389R (1) H369P (1) A98S (1) G2500A (1) I349V (1) I107V (1) V561D (1) C481R (1) L833V (1) P200T (1) G1051A (1) Y93F (1) Y414C (1) Y1248H (1) K65N (1) L74M (1) P4502C (1) Y1248C (1) Y1248D (1) F227R (1) V89L (1) T164I (1) H1124D (1) C94A (1) G1628A (1) A2215D (1) E200K (1) F227L (1) I305F (1) N682S (1) T1010I (1) I655V (1) R885H (1) G7444A (1) R776G (1) E354Q (1) A21443C (1) M351T (1) R620W (1) A54T (1) D594G (1) F311L (1) T49A (1) F116Y (1) H870R (1) G205S (1) E355G (1) R535H (1) I767M (1) L55M (1) E571K (1) L55R (1) M2540A (1) E92K (1) G238A (1) L838P (1) E6V (1) L814P (1) K509I (1) V21I (1) G699A (1) V167F (1) D949V (1) L33P (1) M66V (1) D61804R (1) R849W (1) V762A (1) D816H (1) V108M (1) V326L (1) V411L (1) L10D (1) L58H (1) E158K (1) N334K (1) A1067T (1) S1800A (1) G894T (1) G202A (1) C282T (1) I191V (1) G435A (1) K1060T (1) A10H (1) R272G (1) V654A (1) V106T (1) C1091T (1) I638F (1) P317R (1) V433M (1) S230R (1) N550H (1) R4E (1) P1058A (1) M244V (1) N550K (1) E709Q (1) G304A (1) T124A (1) S253N (1) M680I (1) G1316A (1) M552V (1) M552I (1) R182H (1) D835V (1) A871E (1) D835Y (1) A677G (1) C1950G (1) H1505R (1) A893S (1) L597Q (1) S2808A (1) N55H (1) K28M (1) D89E (1) A38G (1) L485W (1) M9346A (1) L159F (1) A437G (1) R92Q (1) V29C (1) L38V (1) G135C (1) A677V (1) C34T (1) G93R (1) R270H (1) V321A (1) C10D (1) G308V (1) R122W (1) D614G (1) H2507Q (1) D20W (1) G309A (1) G721A (1) G309E (1) I90P (1) C59R (1) C416R (1) G71A (1) Q61R (1) Q61L (1) H835L (1) R498L (1) V941L (1) Q62E (1) R389G (1) D769N (1) G156A (1) E1784K (1) G98T (1) Q65E (1) T92A (1) S239D (1) C656G (1) R451C (1) G73C (1) G5665T (1) R72P (1) F64L (1) L248R (1) M204I (1) R149S (1) A105G (1) M28L (1) D769Y (1) V769M (1) R75T (1) E193K (1) T890M (1) P250R (1) P58A (1) L532S (1) S147G (1) S1235R (1) K660E (1) T454A (1) R76K (1) L1213V (1) V742I (1) V1238I (1) R74W (1) T102C (1) K3048A (1) T93M (1) D961S (1) G1269A (1) R277W (1) P187S (1) Q20W (1) A561P (1) V740A (1) T783I (1) T674I (1) T783A (1) S8814A (1) V90I (1) C325G (1) Q188R (1) R30H (1) C785T (1) S100A (1) R496L (1) G174S (1) L798F (1) V765A (1) P11A (1) C18S (1) L798H (1) G1049R (1) V765M (1) S366T (1) R230C (1) G1376T (1) H396R (1) H396P (1) S65D (1) T1191I (1) A277G (1) L755A (1) H131R (1) T878A (1) T854A (1) P253R (1) C1494T (1) L755P (1) P120H (1) E525K (1) C102T (1) Y1253D (1) G196A (1) A145T (1) K70N (1) L861G (1) H43R (1) I76V (1) C344T (1) F1174V (1) R677W (1) S9313A (1) I112T (1) G10V (1) R10C (1) F1174L (1) R10A (1) K860I (1) R34P (1) F1174C (1) R108K (1) I112M (1) V151I (1) I332E (1) S1369A (1) R32Q (1) N409S (1) C563T (1) Q24H (1) I113T (1) D761Y (1) N291S (1) Y114C (1) V151A (1) G34A (1) G1069R (1) R896C (1) S567L (1) A827G (1) G12S (1) I54T (1) D565H (1) Y113H (1) P367L (1) R102G (1) R368H (1) M3002A (1) P125A (1) V282M (1) M1040E (1) E545G (1) E545A (1) G398A (1) E545D (1) G12A (1) L409P (1) S1787N (1) S784P (1) L841V (1) R14C (1) V943A (1) S9333A (1) Q148K (1) Q148E (1) M1043I (1) Y220C (1) T416P (1) A3669G (1) R38H (1) T961C (1) V1110L (1) T961G (1) L84F (1) S108N (1) C365Y (1) A719G (1) D237E (1) G37R (1) D104N (1) S653C (1) S786I (1) V834I (1) Y376C (1) G3514C (1) G594A (1) G1947A (1) G190C (1) V834L (1) Q546R (1) F522C (1) Q546L (1) Q546K (1) P699S (1) F2004L (1) D101H (1) T393C (1) A1330T (1) R988C (1) H48Q (1) T174M (1) A62V (1) G595R (1) A62T (1) L84V (1) M165I (1) V222A (1) P479L (1) G908R (1) Y318F (1) V75M (1) D101Y (1) I10F (1) D90V (1) H1112L (1) G269S (1) R3500Q (1) V30A (1) S282R (1) D919G (1) I665V (1) H1112Y (1) D90A (1) C385A (1) M95L (1) G1170S (1) V244M (1) G17T (1) S26E (1) N251K (1) W574C (1) G464V (1) C807T (1) V77I (1) Y449D (1) C168H (1) D4064A (1) M50I (1) Q215S (1) F106C (1) K56M (1) G465R (1) G598V (1) S769N (1) E586K (1) T1482I (1) L1196M (1) E148Q (1) T12W (1) S720P (1) Y641S (1) S768R (1) F129L (1) Y641N (1) C938A (1) C165V (1) R19C (1) C383R (1) Y641H (1) C805S (1) Y641F (1) W64R (1) Y641C (1) H1047Y (1) M1268T (1) A736V (1) C61G (1) P1009S (1) V481F (1) S1612C (1) Q546E (1) L718P (1) V179F (1) G106R (1) M1002A (1) P300D (1) S131F (1) N63L (1) W21C (1) L144S (1) M1149T (1) H558R (1) S373C (1) A69S (1) V1180L (1) V774A (1) T377M (1) V689M (1) V774M (1) D164V (1) L387M (1) R199W (1) N86S (1) M694V (1) N86Y (1) G11053T (1) R175H (1) T17M (1) Y86N (1) A2144G (1) A2059G (1) N345K (1) D50W (1) I180V (1) A864V (1) L24E (1) V118I (1) G212S (1) I843S (1) N1303K (1) R1623Q (1) A1033V (1) L1198F (1) N1325S (1) Q812R (1) V773M (1) G212A (1) A997T (1) S241T (1) E167K (1) G1764A (1) G80A (1) E62D (1) E274Q (1) M34T (1) G401S (1) A2142C (1) G1631D (1) G211A (1) D76Y (1) D76N (1) E384G (1) V249I (1) M1106C (1) L234I (1) L101I (1) A2143C (1) K806E (1) A687V (1) A119S (1) P1028S (1) A313G (1) D824V (1) S9C (1) C182A (1) S9G (1) S153F (1) S1900E (1) S1900D (1) S1900C (1) R1644H (1) S1900A (1) R702W (1) T1456G (1) T1565C (1) E1021K (1) K15210D (1) G779C (1) G82S (1) G779F (1) G840A (1) V18M (1) A27L (1) L28M (1) T351I (1) K121Q (1) L28P (1) H180Q (1) G779S (1) M11T (1) M11Q (1) P549S (1) N215S (1) G60D (1) R352W (1) G623R (1) G84E (1) E161K (1) G951A (1) C23S (1) E184K (1) V1206L (1) Y842C (1) V736A (1) L432V (1) E89Q (1) R135W (1) Y253F (1) G843D (1) D820Y (1) F77L (1) S311C (1) D10W (1) Y143H (1) G86R (1) Y143C (1) R112H (1) Y143A (1) A227G (1) K101Q (1) R463C (1) G85E (1) L236P (1) A310V (1) T798M (1) S310Y (1) R222C (1) A4917G (1) T798I (1) E44D (1) L302P (1) Q30R (1) L786V (1) R287Q (1) P286R (1) D36Y (1) R263Q (1) T599I (1) K103M (1) S680N (1) K1270A (1) R88Q (1) T224M (1) P46L (1) N700D (1) A5147S (1) E21G (1) Y822D (1) Q260A (1) Y188H (1) R131H (1) R1070Q (1) C316N (1) T81C (1) T1304M (1) I167V (1) I82A (1) D13H (1) Q54H (1) Q30H (1) L239R (1) Y823D (1) T117S (1) I84T (1) A222V (1) L106V (1) K432Q (1) G163S (1) I1370K (1) G163E (1) K650E (1) E757A (1) R399Q (1) G41S (1) C1895T (1) P392L (1) T334G (1) H274Y (1) R399G (1)

SNPMiner SNPMiner Trials (Home Page)


Report for Mutation D299G

Developed by Shray Alag, 2020-2021.
SNP Clinical Trial Gene

There are 6 clinical trials

Clinical Trials


1 Prospective Lung Transplant Database for Genetic Research

This study will create a database of clinical and biological research for use in future studies, with information obtained from lung transplant recipients. The database will consist of genetic material and clinical outcomes to be used in future genotyping studies, that is, studies regarding the genetic makeup of individuals. Lung transplantation has become an important option for patients with advanced lung disease. More than 10,000 patients have received them to date, and about 1,200 transplant operations are performed worldwide each year. Although short-term survival has continued to improve, the 5-year survival rate is less than 50 percent. Most post transplant deaths are directly or directly caused by chronic lung rejection, a condition of scarring that worsens lung function. Patients evaluated for lung transplants at Duke University Medical Center may be eligible for this study. For developing the database, a small amount of blood, about 3 tablespoons, will be collected from patients. Blood collection for the research will be done at the same time as blood is drawn for necessary tests. The blood cells and DNA (which contains genetic material) will be isolated for analysis. Patients' DNA samples collected will be identified by a code, and all other identifying information will be removed. Patients may be asked to donate additional blood samples after their lung transplant if researchers would like to reexamine their blood. This study will not have a direct benefit for participants. However, during the study, if it is found that any patients have an inherited risk for a disease likely to cause early death if the disease is not treated, then the researchers will attempt to notify those patients. Overall, it is hoped that information gained during this study will help medical professionals to learn more about immune activation and to see how the reactivity of lung transplant patients changes over time. If specific genetic risks could be identified, it might lead to individualized treatments that work on the immune system. Short-term and long-term survival of lung transplant recipients may thus be improved.

NCT00339209
Conditions
  1. Lung Transplantation Rejection

We recently completed a study that demonstrated two single nucleotide polymorphisms (SNPs) Asp299Gly and Thr399Ile (polymorphisms of the human Toll 4 gene associated with endotoxin hyporesponsiveness) were associated with decreased acute rejection after lung transplantation. --- Asp299Gly ---


2 The Role of TLR-4 Asp299Gly and Thr399Ile Polymorphisms in Children With Urinary Tack Infections

Purpose So far anatomical abnormalities (mostly congenital) were, in the majority of the patients, associated with urinary track infections. In this study the researchers will try to investigate the role of TLRs as molecular interactions between bacterial virulence and host response. TLRs are important mediators in the development of the natural immunity against bacteria. They recognize microbial pathogen associated molecular patterns and alert the host's immune system to the presence of invading microbes

NCT02021305
Conditions
  1. Urinary Tract Infection
MeSH:Infection Communicable Diseases Urinary Tract Infections

The Role of TLR-4 Asp299Gly and Thr399Ile Polymorphisms in Children With Urinary Tack Infections. --- Asp299Gly ---

2. evaluate the effect of the TLR-gene Asp299Gly and Thr399Ile polymorphisms on the development and clinical severity of urinary tract infections (UTI) in children. --- Asp299Gly ---

Primary Outcomes

Measure: frequency of TLR-4 299, 399 polymorphism and expression of TLR-2 and TLR-4 by monocytes in children with urinary track infection and healthy controls.

Time: 4 years

3 Genetic Variants and Susceptibility to Diseases of Prematurity in Very Low Birth-Weight Infants

The purpose of this study is to determine if sequence variations in genes involved in the development and function of vulnerable organs increases susceptibility to chronic lung disease (CLD) and other diseases affecting premature infants, such as necrotizing enterocolitis (NEC), sepsis, patent ductus arteriosus (PDA) and intraventricular hemorrhage (IVH). The study will also determine whether measurement of certain biomarkers in serum will identify infants who will develop these complications of prematurity. Previous studies from this institution and others have identified genetic variants in some genes, such as toll like receptor genes are associated with higher risk of CLD or NEC. The interaction of these variants with other gene variants that can influence the risk of these diseases remains unclear.

NCT00710112
Conditions
  1. Chronic Lung Disease
Interventions
  1. Genetic: gene variations
MeSH:Lung Diseases Birth Weight
HPO:Abnormal lung morphology

Our hypothesis will be tested in VLBW infants in four specific aims: (1) To determine whether the presence of previously described single nucleotide polymorphisms (SNPs) in TLR4 (Asp299Gly, Thr399Ile) TLR2 (Arg753Gln) and TLR5 (Arg392STOP) genes is associated with an increased risk of CLD ; (2) to detect by DNA sequencing if novel genetic variations in TLR4, TLR2, TLR9, MyD88 and other innate immune genes increases the risk of CLD or other disease in premature infants; (3) to identify by gene sequence approach whether variants in other repair and growth genes alter susceptibility to diseases affecting premature infants such as CLD,NEC or sepsis or PDA or IVH; and (4) whether alterations in cytokines, miRNA and other biomarker levels in serum from the same blood samples can provide additional predictive value in recognizing the risk of diseases of prematurity. --- Asp299Gly ---

The TLR4 (Asp299Gly, Thr399Ile) TLR2 (Arg753Gln) and TLR5 (Arg392STOP) SNPs will be evaluated using a multiplex Single Base extension based technique, using commercially available primers. --- Asp299Gly ---

Primary Outcomes

Measure: To determine if small variations in certain genes predispose infants to the development of chronic lung disease and other diseases of prematurity

Time: participants will be followed for the duration of hospital stay, an expected average of 6 to 8 weeks

4 Nitric Oxide, LPS and the Pathogenesis of Asthma - Phase II

The purpose of the study is to determine the role of nitric oxide (NO) in asthma and to characterize the symptoms associated with inhaled endotoxin (lipopolysaccharide [LPS]) in normal subjects. In this study, we will determine the effect of inhaled endotoxin on exhaled NO in healthy African Americans, with and without NOS2 promoter polymorphisms. The protocol described in this submission will involve the use of NIH Clinical Center Reference Endotoxin which has been approved by the FDA under IND BB-IND-10035.

NCT00643058
Conditions
  1. Healthy
Interventions
  1. Biological: LPS endotoxin

Because SNPs in the TLR4 gene result in a lack of airway obstruction in response to endotoxin, we will genotype the 1000 DNA samples for the Asp299Gly and Thr399Ile TLR4 polymorphisms in Phase 1 and exclude these individuals from the studies proposed in Phase 2. Likewise, CD14 serves as a coreceptor for endotoxin and polymorphisms in the CD14 gene and promoter have been associated with asthma and responsiveness to endotoxin. --- Asp299Gly ---

Primary Outcomes

Measure: Differential response to inhaled LPS based on NOS2 inhibition.

Time: 24 hours with optional 48 hr,72hr and 7 day follow up

Secondary Outcomes

Measure: Physiologic measurements

Time: 24 hours with optional return up at 48 hrs, 72hrs and 7 day follow up

5 TLR4 Polymorphisms and Predisposition for Skin Cancer Development

Toll-like receptors (TLRs) play a key role in the innate immune system. Toll-like receptor-4 (TLR4) in particular, appears to play a role in susceptibility to cancer. Of 44 identified SNPs (small nucleotide polymorphisms) in TLR4, the most common is an A-G substitution at nucleotide position +896, downstream of the cDNA start codon, a missense mutation which leads to an amino acid substitution Asp299Gly in the third exon of the TLR4 gene. Pre-clinical studies from our laboratory have shown an association of TLR4 with ultraviolet radiation induced skin cancer. Hence, in this study we will assess the pattern of TLR4 polymorphisms and susceptibility to skin cancer.

NCT03122366
Conditions
  1. Skin Cancer
Interventions
  1. Diagnostic Test: Detection of single nucleotide polymorphisms (SNP)
MeSH:Skin Neoplasms
HPO:Neoplasm of the skin

Of 44 identified SNPs (small nucleotide polymorphisms) in TLR4, the most common is an A-G substitution at nucleotide position +896, downstream of the cDNA start codon, a missense mutation which leads to an amino acid substitution Asp299Gly in the third exon of the TLR4 gene. --- Asp299Gly ---

TLR4 SNP Asp299Gly. --- Asp299Gly ---

Primary Outcomes

Description: TLR4 SNP Asp299Gly

Measure: single nucleotide polymorphism

Time: once during the course of study

6 Role of TLR4 in Environmental Asthma

The overall goal of this project is to identify genes that are involved in the development of airflow obstruction and airway inflammation in asthmatics, and to determine whether polymorphisms in these differentially expressed genes predispose individuals to develop asthma. In this project, we hypothesize that polymorphisms of genes expressed by the airway epithelia in asthmatics following specific airway challenges predispose individuals to the development of asthma.

NCT00671892
Conditions
  1. Asthma
Interventions
  1. Biological: Lipopolysaccharide endotoxin
MeSH:Asthma
HPO:Asthma

We hypothesize that individuals with the co-segregating Asp299Gly and Thr399Ile mutations in the TLR4 gene will exhibit a defective immune response to LPS, and that specific components of altered immunity in these individuals are linked to characteristic airway responses to LPS. Specific Aim 1: Approximately 1000 individuals will be genotyped in order to establish 3 study groups: 10 subjects homozygous for the TLR4 299/399 mutation; 10 subjects heterozygous for the TLR4 299/399 mutation; and 10 subjects homozygous for wild type TLR 4. Specific Aim 2: Ten individuals with wild type TLR4, 10 individuals heterozygous for mutant TLR4 and 10 individuals homozygous for mutant TLR4 will be phenotyped for airway responsiveness to inhaled LPS. --- Asp299Gly ---

Primary Outcomes

Measure: Ascertain individuals homozygous, and heterozygous for mutant TLR4 genotype, along with wild types by recruitment of healthy screening subjects in the community.

Time: completed

Secondary Outcomes

Measure: Assess the effect of TLR4 genotype on LPS endotoxin induced immune responses and assess the association of the LPS-induced immune response with LPS-induced airway responses.

Time: 24 hours


HPO Nodes


HP:0002088: Abnormal lung morphology
Genes 1425
KMT2D SMARCB1 ABCA12 MAT2A TNFSF11 TRAIP MAGEL2 DNAAF1 NFE2L2 MITF NFKB2 LCK MAGEL2 SGCG ALG9 TECPR2 GTF2IRD1 CALCRL KAT6B CHAMP1 OFD1 CTRC SCNN1G CD247 MGP TGFBR2 SPINK5 CTPS1 RASA2 NHLRC2 PHGDH RTEL1 NTRK1 NGLY1 ARVCF SLC2A10 RELB ZNF341 RSPH9 FCN3 NELFA RREB1 NAA10 MALT1 HPGD CFTR GLI1 OCA2 LETM1 NPHP3 PIK3CD FSHR FMO3 USP9X TCF4 WDR35 PRSS1 HLA-DPA1 DNAH11 RIT1 ZAP70 STK11 NKX2-5 UNC119 CDC45 BUB1B SNAI2 WAS SIM1 GNPTAB DYNC2H1 FOXH1 CFAP221 TARS1 NF1 NEB LAMB2 TTC7A CCR6 RARA ACTL6B MYO5A CD81 ADNP TNFRSF13B SEC24C TBX1 MYH6 COL3A1 TSC1 CYBA HLA-DPB1 TERT GNS FOXH1 EVC2 LIPN KATNIP TPM2 RRAS2 TSC1 EPHB4 COL6A1 NIPBL SPAG1 FLNB IL17RA HSPG2 ITGA8 GAS1 SLC12A6 EFEMP2 CRLF1 SLC26A2 GMNN DGCR8 ACTA2 CTLA4 SLC35A1 ADAMTS3 TAPBP SLC25A24 PRKCD SPECC1L CCR6 CXCR4 HOXD13 BLM RNU4ATAC CFAP300 FOXP1 CDON CD79A TTC21B CBL RAG1 VPS51 DISP1 USB1 NUP107 NEPRO COL11A2 FLNA CR2 ACVRL1 LAMTOR2 NEK1 SNORD115-1 GLE1 MAP3K20 DNMT3B SLC26A2 FAS MKRN3-AS1 LYST PIK3R1 ACADVL LIFR TDGF1 TAPT1 RFX5 VPS33A MYRF MDM4 HRAS TBC1D24 NGLY1 GLI2 FGF8 ODAD4 CCDC40 MYH11 C11ORF95 MCM4 CTLA4 CRELD1 ZBTB24 TINF2 ECM1 CAV1 NAA10 LRRC6 PUF60 CFTR FLCN COL11A2 CR2 FOXE1 CCBE1 ELP1 TFRC AGA SMPD1 PWRN1 MMP21 IPW GATA6 LACC1 TCIRG1 SERPINF2 BLNK IFT80 FLI1 UBB KIF20A STAT1 DLL4 MBTPS2 PAX3 ELP1 SNRPN DISP1 RMRP TGFBR2 KRAS STAG2 IRF8 SIX3 SOX10 KIF1A RYR1 IGHM BTK NOTCH3 DICER1 CYP4F22 CXCR4 RSPH1 MEFV CCBE1 DNAH11 ZIC2 WDFY3 CCND1 CSF2RA POLR3A BCL6 LAMA2 SMAD4 SKIV2L STAT1 SNX10 TERT FGF8 BRAF SFTPC FOXJ1 ATP11A AICDA SHH RYR1 ODAD1 SCARB2 SIK1 HACD1 CHRNG CREBBP TNFRSF13B CITED2 OCA2 MYBPC3 NODAL NOTCH2 CFAP298 SELENON CEP57 CTLA4 TRIM28 ZIC2 ALMS1 DOK7 ODAD4 IDUA DLL1 ELN SBDS COG6 TBX6 RFXAP PEX13 TCTN3 PTPN22 DGCR6 SFTPC RAG1 INTU EDNRB FGF20 MAGEL2 DNASE1L3 RASGRP1 STRA6 IFT81 COG4 MARS1 EPM2A MESP2 TTC12 SOS1 TBC1D23 IL12A-AS1 ENG SCNN1B CSF2RA TGFB1 CCN2 FBXW11 MAN2B1 HLA-DRB1 PTCH1 NPM1 EPG5 UGP2 GLI2 GAS2L2 TSC2 PPP1CB RANBP2 SCN11A GPKOW CBL CTLA4 IL12A MESP2 IL21R CRELD1 IL17RC UMPS TERT SLC18A3 MYSM1 DSE TRPS1 PEX1 MKRN3 RTEL1 RPGR DYNC2H1 PRKG1 DSG1 ACP5 FLT4 JAK3 TCF20 EXOSC9 MIR140 DNAL1 NCF4 ACTC1 IFT80 FGFR3 ALG14 VAMP1 RTL1 ESS2 WRN TGFB1 MKS1 DYNC2LI1 EWSR1 FGF20 CD3E POU6F2 ELN IDUA SFTPA2 SFTPB ATP5F1A FANCF PLCG2 SLC29A3 NDN PIGL RAG2 RAG2 SLC46A1 SLC2A10 RET PGM3 GBA IL2RG SULT2B1 DNAJB13 JMJD1C TP53 SDR9C7 BUB1 MSN MYOD1 FCGR3A SHROOM4 PNP COQ7 ACTA1 ERF MYSM1 ZEB2 ETFDH AGTR1 LEPR TBX1 PIGT FLNC DGCR2 NCF4 ODAD2 IFT172 RFXANK KAT6B DNAI1 GBA NEK10 DNAI1 KIAA0586 MPLKIP CCNQ MDM2 AGA LAMC2 RAG2 LEPR IL17F DCLRE1C SPIDR LIMK1 PEPD CCN2 ITGA3 MYT1L ZBTB24 STAT5B NCF1 CD3D EP300 RIT1 IL2RB GLI2 DICER1 COL6A3 FBLN5 TASP1 DCLRE1C FARSA CDC42 PYROXD1 IL7R TBC1D24 PLCG2 GAA ODAD3 STAT4 LTBP4 NFKBIA PKHD1 IL17RA KRAS MCTP2 BPTF IGLL1 SCNN1A ODAD3 TK2 PSMC3IP TPM3 RNF113A MBTPS2 IGHM PDGFRB RAF1 FASLG CCDC39 MUSK FAM111B NDUFAF6 TRIP4 MS4A1 SMN1 MUSK PRKAG2 SMARCC2 HLA-DRB1 CFH LEP CYBB LMNA PSMD12 NEU1 CD3E PTPRC STAT3 PLG CHRNA1 FOXH1 TNNI3 PRKAR1A TYK2 LOX FLCN NEK9 ORC6 RNF168 PTPN11 CARD11 CD3G LONP1 TGFBR1 CC2D2A GNPTAB IDUA TREX1 CYBB NBN NRAS LPIN2 DNAAF6 TGIF1 WAC ADA FBN1 STAT3 SETBP1 ACTA1 STRA6 CD3D STAT3 ZMIZ1 ETFB RSPH4A SFTPC HLA-B TBX5 TSC1 DNMT3B A2ML1 RPL10 RPL10 MEFV TP53 ITCH BRCA2 IRF2BP2 GAS1 ASXL1 NEK10 CCDC22 SAMD9 MYH7 WNT4 DOCK3 CD247 CFI RCBTB1 UFD1 TREX1 ASAH1 INPPL1 NOTCH2 SERPINF2 MECP2 DKC1 KAT6B MEFV GLDN CHRNG HYDIN CDT1 DNAAF2 IL6R LAMB3 NFKB1 RUNX2 IL1RN GLI3 IRAK1 KANSL1 DLL3 PTCH1 TGFBR1 NDUFB10 REN TDGF1 ABCA3 RAG1 KIF11 FGFR1 UBE2A MYOD1 NFKB2 PIK3CD SMN1 FREM2 TGIF1 LAT HELLS ZEB2 RSPH9 NSDHL SERPINH1 MTHFD1 FAM13A SETD2 PAX6 SOX18 SMARCD1 OCRL SLC52A3 BMPR2 DZIP1L TDGF1 WDR1 ALB CD28 ADA2 RAPSN DLL1 RBPJ WDR19 HLA-DRB1 SHH BMPER MYLK TMEM94 SIX3 PML TGFB3 MYL2 STAG2 TBL1XR1 FBN1 EFL1 TERC BUB3 HES7 FOXC2 RBM10 CFAP410 MASP2 TRIP13 GLB1 MEG3 MYH3 LIG4 PARN RHOH NFKB2 EDARADD DNAAF6 BCR RNF125 TLL1 DCLRE1C SCNN1A GPC3 ASAH1 SNAP25 NR5A1 NHP2 DNAAF5 DLL1 EXTL3 PRPS1 MAN2B1 FANCB COMT ZMYND10 FOXN1 PRKCD BLNK NTNG1 IL2RG IL7R EMG1 TRPV4 SMPD1 ETFA IRF5 NODAL WT1 NECTIN1 LAMTOR2 RAG2 ROR2 ADA FCGR2A IER3IP1 CYTB KDM6A BTNL2 WNT3 TLL1 ALOXE3 TGIF1 ASCC1 PIGN BNC1 RIPPLY2 BAP1 NOS1 NXN DSP DNAH1 ITPR1 IGH PIEZO1 CSPP1 COL3A1 ARHGAP31 MS4A1 NODAL USB1 LRRC56 NPM1 TSC2 ATP6V0A2 DHCR7 ZBTB16 EPG5 TINF2 CASP8 PRPS1 IKBKB ARID2 SHH ARID1B RLIM EGFR CDKN2A LAMA3 SFTPA1 IKZF1 CAV1 PLOD1 PRKDC LMNA JAK3 BMP2 AKT1 CFTR ELN AGT DNAAF4 ATP6V1E1 IFT140 BTK BTNL2 COPA PEPD SCNN1B KCNJ6 GAA MCIDAS PTEN SOX4 ZMYND10 UNG GATA6 DYNC2I1 PSAT1 GATA4 SLC26A2 NDN BCOR NAB2 CD81 NKX2-1 PLOD1 PLEC FUZ CRTAP FGF8 GAS1 ABCA12 REST B3GLCT IGH CLIP2 SCNN1B H19 CYBC1 ELN RAG1 ALDH18A1 MYT1L KLHL41 ACE RSPO2 CLEC7A HIRA GP1BB DRC1 GDF1 TP53 GLI3 SVBP TCIRG1 FRAS1 IRF5 GDF1 PMM2 PAFAH1B1 ZMPSTE24 TGM1 DLL1 SIX3 CCNQ TIMM8A ELN PTEN FUCA1 MYD88 SPAG1 ARID1B AGGF1 THOC2 ABCA3 ARSB CFB PORCN HFE SOX11 NOTCH1 FOXP3 TERC USP9X P4HTM DRC1 AP3B1 CBL POLA1 CDON PKHD1 TAF1 COLQ SON TRPV3 TSC1 DVL3 TCF3 TRIP4 CHEK2 FLNB STAT5B STXBP2 CREBBP NPAP1 FAM20C STK36 DOCK8 SLC7A7 DDR2 TTC37 CD8A DOCK6 CD46 CCDC65 BCL2 INPPL1 DIS3L2 MFAP5 TNFRSF13C KNSTRN RPS15A GLA SELENON LRRC6 KMT2E SLC5A7 TERT GRIP1 DYNC2I2 PTPN22 FAT4 SHH IFIH1 IL7R PARN ARHGAP31 CSF2RB CHST14 TANC2 CIITA ZIC2 FLNA G6PC3 MARS1 BACH2 ZNHIT3 DNAJC21 SH2D1A CCNO COL13A1 DISP1 IL21 HYDIN MGP IL2RA MED25 GSN FOXH1 SLC35C1 PNP PRTN3 SP110 ARID1A MEFV NOD2 SERPINA1 NHP2 MED13 FRAS1 NBN MCIDAS FCGR2B KLHL40 BLM RAG1 RRAS TAP1 SNRPN ADGRG6 NADK2 SLC26A2 DDR2 ZAP70 MAGT1 FGFR1 GATA2 ALOX12B TMEM260 IFNGR1 SMAD4 SLC7A7 NFKB1 RB1 RARB APOE GATA6 DOCK8 AP3D1 SOS2 STING1 CASP10 B2M FLCN SRP54 ZEB2 TNFRSF13C FADD C4A TTC12 TAP2 KPTN STN1 LBR SNRPN DNAI2 MRAS COL2A1 RNF168 CHRM3 CCNO CHRNG RAC1 FGFR3 LGI4 ADA NUP88 TBX20 ODAD2 BCL10 FLNA SLC25A22 ELN SMO GBA TGFB2 NUMA1 RAG2 GATA4 DNAH9 SMARCA4 TNFRSF11A IRAK4 GUSB CD40LG SCNN1G SLC34A2 DHCR7 MIF GUSB KITLG KIAA0586 GRIP1 NSD2 DPF2 SLC35A1 EIF2AK4 GBA SPP1 NCF2 MKKS GAS2L2 MYH3 TBCD HLA-DRB1 PTPN22 RAC2 DDX6 CEP57 RELA PTCH1 DNAI2 ZFPM2 TPP2 RAG1 STAT6 IFT43 KANSL1 PURA LRRC56 DNAAF1 SCNN1G IL6ST ACP5 XIAP IL2RG FANCB IGLL1 AFF4 SCNN1B BCORL1 BTK PCNT MUC5B MRPS22 CDON COG4 PRKCD PTPN11 LRRC8A PHGDH BGN DVL3 PSAP HLA-DQA1 DYNC2I2 SLC35C1 PWAR1 SLC1A4 CR2 TBCE AGRN CTCF FBLN5 VANGL1 TRIP11 NKX2-5 TSC2 GFI1 TNFSF12 GAS8 MAPK1 SLC11A1 IFNG FBN1 DNAAF2 SCNN1A ACTA1 MESP2 HABP2 NDN SLCO2A1 FOXE3 IDS PANK2 FGFR1 CHD7 DNAAF3 NABP1 DNAAF3 CFI DPM2 OCA2 PCGF2 SFTPB MANBA TNNT2 SRP54 PLVAP CD79B SOX18 INVS DYNC2LI1 RARB CD19 FOXJ1 BMPR2 PIGN LEP PKD1L1 NHLRC1 GPC6 ITCH APC2 GATA6 SCNN1A SERPINA1 ATM GBA DNAJB13 CEP120 TNFRSF1A KIAA0319L CLCN7 NSD1 CACNA1C SPEF2 PIEZO2 DYNC2I1 NKX2-5 CREBBP TBX1 TNFSF12 COL6A2 EFEMP2 RAC2 PRSS2 TBL2 CFTR IL10 CFAP298 DONSON RSPH3 ABL1 EVC SDCCAG8 DNAH5 WIPF1 PARN PDGFRA TINF2 NCF2 TNFRSF1B CEP120 FOXP1 RFC2 NPHP3 BCOR GATA4 SNORD116-1 POLR2A NOP10 CCDC103 OFD1 DNAAF5 GATA6 IL6 POLA1 PDHA1 LMNA CD19 SFTPC SIX3 LTBP3 SMPD1 SMARCD2 RIPK4 CSF2RB PSMB8 HPS4 CRKL PTH1R EP300 RSPH1 PERP ATM ABCA3 DCTN4 CLCA4 CTSC STAT3 CCND1 POLR3H TRIP13 FCGR2A MST1 MUC5B DNAH5 CDON TRAF3IP2 IDS SRSF2 SLC18A3 TRIM28 CD79A PIK3R1 GRHL3 NOP10 HPS6 WNT3 RPGR DPP9 RAF1 SCNN1G CD79B RSPO2 BCL11B IVNS1ABP ACTL6A ZIC2 AFF4 SMAD3 ITGA7 CITED2 ERCC2 RAB3GAP2 TRIP11 IL23R SPINK1 TERC RTEL1 CYBA TSC2 CITED2 GLE1 GPC3 TGFB2 SCN9A RASGRP1 FGF8 SNRPN DYNC2I1 CARD11 POLE ICOS FADD NME8 HLA-DQB1 LMNA PGM3 EOGT CDCA7 WT1 SAMD9L SMC1A ICOS GLI3 SREBF1 CHAT RFX5 FOXF1 TDGF1 CHST14 CCDC40 SMARCE1 DCLRE1C ALMS1 TLR4 NCF1 RSPH3 CYBC1 SLC25A1 PTCH1 IL2RG B3GALT6 GLI2 GAS1 TNFRSF13B TET2 NRAS WAS ZMPSTE24 EHMT1 WRAP53 FAS WDR35 HPS1 NSMCE3 TGIF1 GLUL SH3KBP1 RFXAP CARMIL2 BCOR GTF2I TNFRSF1A MAGEL2 STAT4 HGSNAT SMAD3 FBLN5 MYO9A GTF2H5 NEK8 TERT RUNX1 RYR1 FAT4 CLPB RIPK1 COL13A1 JAGN1 CIITA TBX20 CSPP1 DNAAF4 CCR1 HK1 MINPP1 UBAC2 NFIX RNU4ATAC BIRC3 WNT4 IKBKB CD27 FAS NLRC4 SFTPA2 NDN AARS2 TGFB1 DHCR24 PIK3R1 HYLS1 CREBBP CHRND ALPL ITK VHL CCDC103 GREB1L ERAP1 FARSB RAB27A NAGLU ODAD1 CTC1 ZCCHC8 TRMT1 SNRPN CEP55 PRPS1 DLL3 LYST KEAP1 GBA JAG1 NME8 MYPN STX1A TNFRSF13C FIP1L1 HERC2 ELANE CORO1A SYT2 CCDC39 CFTR GPC4 ITGA8 ICOS RFXANK KLRC4 DNASE1 DICER1 EP300 PRKAR1A MAGEL2 MLXIPL LZTR1 PIGN BMP15 HLA-DRB1 COL2A1 ADAMTS2 WDR19 ALG12 AK2 CD55 HLA-DRB1 GAS8 DKC1 NKX2-1 DLK1 SCN10A DYNC2I2 HELLPAR LMOD3 FLCN WT1 NODAL LRBA ELANE GTF2E2 SGSH GPR35 BAZ1B SFTPB TRAPPC4 PLP1 CACNA1B RSPH4A FSHR TERT CCDC65 WT1 TERC MID1 NR2F2 DHCR24 ERCC3 WASHC5 NIPAL4 LFNG VPS33A CD19 RLIM GALNS OSTM1 XIAP ASAH1 HLA-B DISP1 NAA10
HP:0008069: Neoplasm of the skin
Genes 287
FERMT1 TYR BAP1 TNFRSF4 MSH2 COL7A1 CDK4 RPS20 MC1R TINF2 WRN KRAS SMO COL7A1 DDB2 CDKN2A KRT16 PSENEN IL7 APC LAMA3 POLH VEGFC LMNA KRT17 FCN3 GJC2 MSH3 HPGD RECQL4 CREBBP COL7A1 KIT PDGFB PTEN KRT16 SDHC EPCAM PTEN XPA TMC6 GJB6 MLH1 HRAS SUFU TGFBR2 PTCH1 CTNNB1 TNFRSF1B WNT10A MPLKIP CDKN2A IL6 GJB2 TP53 LAMC2 TARS1 NF1 FH GNA14 DCLRE1C NF1 WRAP53 NTHL1 KRAS SMARCE1 FH BAP1 ERCC3 EP300 FDPS ERCC4 MVK PIK3CA PERP PMS1 CTSC PORCN ALX3 NUTM1 ING1 PMS2 KIT SLX4 IGLL1 SEC23B RASA1 CD28 HRAS TRPV3 KLLN AKT1 TSC1 PTCH1 KRT17 TCF3 RNF113A MBTPS2 IGHM PDGFRB MEN1 CD79A PIK3R1 FASLG KDSR NRAS IL7 CYLD TMC8 CD79B WNT10A KRT17 COL1A1 IVNS1ABP DOCK8 PRKCD PTCH1 NRAS ERCC3 KRT14 CXCR4 KRT5 ERCC2 MLH1 BLM MITF NRAS KRAS KIT APC TERC NF1 FLCN TERT TNFRSF1B CDKN2A DCC ERCC2 TSC2 SLC17A9 USF3 NF1 NTHL1 FAS PRKAR1A KIT SNAI2 PIK3CA LMNA HRAS IKBKG FAN1 BRD4 RSPO1 TP53 SDHC GJA1 BLM RNF6 FH MSH2 SLC45A2 TERT CIB1 GJB3 TNFRSF10B PIK3CA ECM1 ERCC2 SEMA4A KRT6B DMPK SEC23B PMVK ERCC5 GJB4 TGFBR2 SMO NF2 NF2 RMRP FAS MLH1 CARMIL2 MVD PDGFB SUFU NF2 DKC1 ERCC3 NRAS CASP10 STAT1 PTEN LAMB3 GJB2 BAP1 GTF2H5 RECQL4 DDB2 SMARCB1 CYLD FGFR1 MSH6 NOTCH3 CXCR4 BMPR1A TYR PLCD1 PTCH2 CTLA4 OCRL KRT1 MSH3 MSH2 KRT17 NRAS SDHB KRT6A MC1R CD28 CREBBP CIB1 PIK3CA SDHB STIM1 AKT1 TMC6 KEAP1 AKT1 CTLA4 NLRP1 MLH3 PTCH2 APC KRT6B MLH1 LZTS1 GJB2 CDKN1B KIT TRAF7 DICER1 PTEN MMP1 PRKAR1A KRT9 BMPR1A NF1 MMP1 CTNNB1 RASGRP1 NF1 SPRED1 FLT4 SDHD LRRC8A KLLN GTF2E2 PTEN SASH1 BLNK ANAPC1 PIK3CA GNAS XPC BRAF ERCC4 ERCC3 MSH6 ERCC2 OCA2 KIT ERCC4 IFNG APC GPR143 CYLD FLT4 STK4 POLH ERCC5 WWOX HRAS SLCO2A1 XPC TMC8
SNP 0