SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT00671892

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

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 Asthma
MeSH: Asthma
HPO: Asthma

1 Interventions

Name: Lipopolysaccharide endotoxin

Description: Delivered in nebulized form expressed in activity units(endotoxin units -EU). Subjects receive each dose 30 min after completing the previous dose, dose duration is approximately 10 minutes: Challenge One first saline then 5000 EU 10,000 EU 20,000 EU Challenge 1 and 2 must be at least 2 weeks apart. Challenge 2 Saline 40,000 EU 80,000 EU

Type: Biological

Challenge


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

Purpose: Basic Science

Single Group Assignment


There are 2 SNPs

SNPs


1 D299G

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 ---


2 T399I

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 --- --- Thr399Ile ---



HPO Nodes


HPO:
Asthma
Genes 66
ELOVL4 FLG COL5A1 LIFR COL5A2 TGIF1 LIG4 CDSN ERCC2 BCL11B CARMIL2 COMT SEC24C ALMS1 ARVCF NKX2-1 DOCK8 GLI2 TRAIP NFKB2 CFTR TBX21 SCN4A UFD1 GAS1 PEPD SHH BBS1 GTF2H5 PEX5 CASP8 FGF8 CARD11 FGFR1 TDGF1 PLCG2 LRBA SIK3 COX4I2 IDS PTCH1 RREB1 FOXH1 SIX3 DLL1 ADA SUFU NODAL NSUN2 GRHL2 TALDO1 NEK9 CCDC151 JMJD1C DISP1 TBX1 PGM3 SDHD CDON HIRA ZIC2 GP1BA GP1BB COL1A1 SPINK5 GP9