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30 September 2014 : Research paper

Correlation of PCSK9 Gene Polymorphism with Cerebral Ischemic Stroke in Xinjiang Han and Uygur Populations

Dengfeng HanABCDEF, Jianhua MaABCD, Xiaoning ZhangADG, Jian CaiBC, Jinlan LiBF, Tuerhong TuerxunBF, Chenguang HaoB, Lei DuB, Jing LeiB

DOI: 10.12659/MSM.892091

Med Sci Monit 2014; 20:1758-1767

Abstract

BACKGROUND: Cerebral ischemic stroke (CIS) is a major cause of morbidity and mortality. Its main pathological basis is atherosclerosis (AS); in turn, the main risk factor in AS is dyslipidemia. Human proprotein convertase subtilisin/kexin9 (PCSK9) plays a key role in regulating plasma low-density lipoprotein (LDL) cholesterol levels. We sought to assess the association between PCSK9 and CIS in Chinese Han and Uygur populations.

MATERIAL AND METHODS: We selected 408 CIS patients and 348 control subjects and used a single-base terminal extension (SNaPshot) method to detect the genotypes of the 20 single-nucleotide polymorphisms (SNPs) in PCSK9.

RESULTS: Distribution of SNP8 (rs529787) genotypes showed a significant difference between CIS and control participants (P=0.049). However, when analyzing Han and Uygur populations separately, we found that only Han subjects showed distribution of SNP1 (rs1711503), SNP2 (rs2479408), and SNP8 (rs529787) alleles that was significantly different between CIS and control participants (P=0.028, P=0.013, P=0.006, respectively), and distribution of SNP2 (rs2479408) in the dominant model (CC vs. CG + GG) was significantly different between CIS and control participants (P=0.013), even after adjustment for covariates (OR: 75.262, 95% confidence interval [CI]: 7.232–783.278, P<0.001). Distribution of the 2 haplotypes (A-C and G-C) (rs1711503 and rs2479408) was significantly different between CIS and control participants (both, P=0.011).

CONCLUSIONS: Both rs1711503 and rs2479408 of PCSK9 genes were associated with CIS in the Han population of China. A-C haplotype may be a genetic marker of CIS risk in this population.

Keywords: Case-Control Studies, Brain Ischemia - genetics, Alleles, Ethnic Groups - genetics, Gene Frequency, Genetic Predisposition to Disease, Haplotypes - genetics, Linkage Disequilibrium - genetics, Logistic Models, Polymorphism, Single Nucleotide - genetics, Proprotein Convertases - genetics, Serine Endopeptidases - genetics, Stroke - genetics

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750