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Associations Of Variants In IL-33/ST2Signaling Pathway Genes With Coronary Heart Disease,Essential Hypertension Risk

Posted on:2015-01-05Degree:DoctorType:Dissertation
Country:ChinaCandidate:F Q WuFull Text:PDF
GTID:1224330428965955Subject:Internal Medicine
Abstract/Summary:
Part I Associations between variants in IL-33/ST2signaling pathway genes and coronary heart disease riskObjective:Coronary heart disease (CHD) is a complex chronic disease caused by multiple genetic and environmental factors.The IL-33/ST2signaling pathway plays an important role in CHD. Despite powerful biological and prognostic data describing the role of IL-33/ST2signaling in the development of CHD, there is little information regarding the significance of IL-33/ST2genetic variants in CHD. Here, we examined the association between genetic variants in IL-33, ST2, and IL-1RAcP of the1L-33/ST2axis and the risk of CHD.Methods:We conducted a case-control study of1146CHD cases and1146age-and sex-frequency-matched controls. Twenty-nine single nucleotide polymorphisms (SNPs) in IL-33, ST2, and IL-1RAcP gene were genotyped by Sequenom MassArray and TaqMan assay. Logistic regression was used to analyze these associations.Results:The rs4624606(IL-1RAcP) variant showed significant associations with CHD risk. The AA genotype was associated with a1.85-fold increased risk of CHD (95%confidence interval [CI]=1.01-3.36; P=0.045) compared to the TT genotype. Further analysis showed that AA carriers also had a higher risk of CHD than TT+TA carriers (odds ratio [OR]=1.85;95%CI=1.85-3.35;P=0.043).In stratified analysis, the risk associated with the AA genotype of rs4624606was stronger in patients who had hypertension. However, no significant interactions were observed between rs4624606and traditional CHD risk factors, and no significant association was observed between variants in IL-33/ST2genes and CHD risk.Conclusion:The SNP rs4624606in IL-1RAP was nominally associated with CHD risk. Further studies are needed to replicate our results in other ethnic groups with larger sample sizes. PartⅡ Associations between variants in IL-33/ST2signaling pathway genes and essential hypertension riskObjective:The IL-33/ST2signaling pathway plays an important role in essential hypertension (EH). Our aim was to determine whether genetic variants in IL-33, ST2, and IL-1RAcP of the IL-33/ST2signaling pathway genes are associated with the risk of EH.Methods:We conducted a case-control study of1151patients and1135matched controls.29single nucleotide polymorphisms (SNPs) in IL-33, ST2, and IL-1RAcP gene were genotyped by Sequenom MassArray and TaqMan assay. Logistic regression was used to analyze these associations by additive and dominant models.Results:Four SNPs in ST2gene were significantly associated with EH after adjusting for conventional EH risks factors. The wild-type homozygote of rs3821204, rs11685424and rs12999364were associated with increased EH risk. In contrast, the wild-type homozygote of rs6543116was associated with a decreased risk of EH. The wild-type homozygote of rs16865597in IL-1RAcP gene was also associated with increased EH risk after adjusting for conventional EH risks factors.Conclusion:Four SNPs in ST2gene rs3821204、rs11685424、rsl2999364and rs6543116may contribute to the susceptibility to EH. The SNP rsl6865597in IL-1RAcP gene was also associated with increased EH risk.Further studies are needed to replicate our results in other ethnic groups with larger sample sizes.
Keywords/Search Tags:coronary artery disease, IL-33/ST2signaling pathway, gene, singlenucleotide polymorphismsessential hypertension, singlenucleotide polymorphisms
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