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Association study of C-reactive protein associated gene HNF1A with ischemic stroke in Chinese population.

ABSTRACT: Ischemic stroke is a life-threatening condition due to obstructed blood supply of the brain. Elevation of plasma C-reactive protein, an important inflammatory marker, was known to associate with increased risk of ischemic stroke. Previous studies reported association between genetic variants of HNF1A and plasma level of C-reactive protein. The HNF1A gene encodes a hepatocyte transcription factor which might have regulatory effects on C-reactive protein synthesis in liver. Therefore, the C-reactive protein associated gene HNF1A seems to be a promising candidate gene for ischemic stroke.We used HNF1A as a candidate gene of ischemic stroke and evaluated seven common variants of HNF1A for their contribution to ischemic stroke. The association analysis of HNF1A variants with ischemic stroke was performed in a Chinese population with 918 cases and 979 controls. For total ischemic stroke and large vessel disease subtype, none of variants exceeded significant threshold. For small vessel disease subtype of ischemic stroke, the G allele of rs7953249 showed nominal association (OR?=?0.82, p?=?0.04) after data adjustment for conventional risk factors. However, our preliminary results did not survived bonferroni correction for multiple comparisons.Common genetic variants of HNF1A showed nominal association with small vessel disease subtype of ischemic stroke though not survived bonferroni correction for multiple comparisons. The association between HNF1A and ischemic stroke is limited by small effects of individual SNPs. Our study provided additional genetic evidences to understand the role of HNF1A gene and C-reactive protein underlying ischemic stroke.

SUBMITTER: Shi H

PROVIDER: S-EPMC4962403 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Association study of C-reactive protein associated gene HNF1A with ischemic stroke in Chinese population.

Shi Haibin H Leng Song S Liang Hui H Zheng Yan Y Chen Lidian L Chen Lidian L

BMC medical genetics 20160726 1

<h4>Background</h4>Ischemic stroke is a life-threatening condition due to obstructed blood supply of the brain. Elevation of plasma C-reactive protein, an important inflammatory marker, was known to associate with increased risk of ischemic stroke. Previous studies reported association between genetic variants of HNF1A and plasma level of C-reactive protein. The HNF1A gene encodes a hepatocyte transcription factor which might have regulatory effects on C-reactive protein synthesis in liver. Ther ...[more]

PMID: 27460564

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Project description:Background and purposeIschemic stroke (IS) is the main cause of mortality and disability among the old people in China and is a multifactorial disease influenced by many factors including genetic factors like the allele for CYP 2J2. It has been demonstrated that CYP2J2 polymorphisms alter the transcriptional activity. However, studies on the association between CYP2J2-50G/T polymorphism and IS have reported conflicting results. Thus, our study aimed to examine the association between 4 variants in the CYP2J2 gene and the risk of IS and its subtypes, in the Chinese population.Materials and methodsIn this study, genotyping was performed by using polymerase chain reaction (PCR) sequencing for 202 IS patients and 206 age- and sex-matched controls. Odds ratios (ORs) and confidence interval (CI) were estimated by multivariate logistic regression and PCR results were confirmed by DNA sequencing. A meta-analysis was conducted to evaluate the association of CYP2J2-50G>T polymorphism with the risk of IS in Chinese population by calculating pooled OR.ResultsWe found this polymorphism was significantly associated with IS (17.82% vs. 10.68%, P = 0.039). Multiple logistic regression analysis revealed that GT genotype was associated with a significantly high risk of IS (OR = 2.32, 95% CI: 1.21-4.45, P = 0. 011) after adjustment for other confounding factors such as hypertension, diabetes, heart disease, smoking habit, family history, triglyceride and low-density lipoprotein levels. We also found a significant association of GT genotype with small artery occlusion (SAA) (P < 0.05; OR = 2.22; 95% CI: 1.043-4.72). Meta-analysis results also showed that the GT genotype carriers had a negative effect on the risk of IS in Chinese population with overall OR of 1.40 (95% CI: 1.06-1.84).ConclusionThe findings of the present study suggested that polymorphism in -50G/T position of CYP2J2 gene might be a risk factor for IS in Chinese population. Further large prospective studies were required to confirm these findings.

Dataset Information

Association study of C-reactive protein associated gene HNF1A with ischemic stroke in Chinese population.

Publications

Association study of C-reactive protein associated gene HNF1A with ischemic stroke in Chinese population.

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