Open AccessHeterozygote Genotypes at rs2222823 and rs2811712 SNP Loci are Associated with Cerebral Small Vessel Disease in Han Chinese Population
Author(s) -
Li Wei,
Hu Bo,
Li GuiLin,
Zhao XingQuan,
Xin BaoZhong,
Lin JinXi,
Shen Yuan,
Liang XianHong,
Liu GaiFen,
Gao HanQing,
Liao XiaoLing,
Liang ZhiGang,
Wang YongJun
Publication year - 2012
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/j.1755-5949.2012.00322.x
Subject(s) - odds ratio , single nucleotide polymorphism , snp , genome wide association study , genotype , genetics , heterozygote advantage , medicine , candidate gene , biology , gene
SUMMARY Aims With developments of etiology of cerebral small vessel disease (CSVD) and genome‐wide association study (GWAS) of stroke, the genetic studies of CSVD are focused on genes related to blood‐brain barrier (BBB) and aging. The project aims to investigate the association between CSVD and susceptibility loci and candidate genes. Methods All study subjects admitted Beijing Tiantan Hospital from June 2009 to September 2010 including 197 cerebral small vessel disease patients(S), 198 large artery atherosclerosis control individuals (vascular stenotic rate ≥50% diameter reduction) (L), 200 hypertensive intracerebral hemorrhage control individuals (H) and 197 stroke‐free control individuals (C). 15 SNPs in 4 genes (MYLK, AQP4, NINJ2, and INK4/ARF) were genotyped using Multiplex Snapshot assay. Each SNP was first examined between the groups S and C in different genetic models (codominant, dominant, recessive, overdominant, and log‐additive). Permutation correction was used to adjust for multiple testing. The significant SNP loci were further analyzed in comparing S with L and H, respectively. Subgroup analysis was also performed for each risk‐factor category. Results Among the 15 SNPs, rs2222823 and rs2811712 were found to be significantly associated with CSVD after multiple‐testing adjustment. The heterozygote (A/T) of rs2222823 of MYLK has an odds ratio of 0.52 (95% CI =[0.35, 0.79], P = 0.002, adjusted P = 0.031) when compared with homozygotes. The heterozygote (C/T) of rs2811712 of INK4/ARF has an odds ratio of 1.75 (95% CI =[1.13–2.71], P = 0.004, adjusted P = 0.050). The SNP rs2222823 was significant ( P = 0.035) in comparing S with H. In comparing S versus L, it is significant for the subgroups of patients without diabetes ( P = 0.012) and drinking ( P = 0.018). rs2811712 was significant in comparing S with L for the subgroups of patients with hyperlipidemia ( P = 0.029) and drinking ( P = 0.04). Conclusion The heterozygotes (T/A) at the rs2222823 SNP locus of MYLK gene decreases the risk of having cerebral small vessel disease, while the heterozygotes (C/T) at the rs2811712 SNP locus of INK4/ARF gene increases the risk, suggesting that the MYLK and INK4/ARF are the associated genes of cerebral small vessel disease in Han Chinese population.