The research on association of copy number variation in chromosome 9p21 region with atherothrombotic stroke in the Han Chinese population

J Neurol Sci. 2017 Jun 15:377:88-94. doi: 10.1016/j.jns.2017.04.001. Epub 2017 Apr 5.

Abstract

Background/purpose: The copy number variants (CNVs) contain more genetic information compared with SNPs. The aim of this study was to elucidate whether the CNVs in Chromosome 9p21 region are associated with increased risk of Atherothrombotic stroke (ATS) in a Han Chinese population.

Methods: A case-controlled association study was conducted in which only patients with ATS were enrolled. The CNVs were detected by the method of multiplex competitive amplification. The differences in distribution of CNVs between cases and controls were analyzed using univariate and multivariate logistic regression analysis. Subgroup analyses were also carried out to determine whether the effect of the CNVs was specific to age and gender among the subjects.

Results: A total of 274 ATS patients and 282 health controls were included in the present study. 4 genes (ANRIL, CDKN2A, CDKN2B, and MTAP) including eight gene fragments in all were analyzed for CNV. The results showed that the copied number of most CNV in the 4 genes is two. There was no significant difference of CNV frequency between groups.

Conclusions: The obtained data suggested a negative association between CNV of the four genes and ATS. It is necessary to perform sequencing analyses across the entire 9p21 region for detecting rare or uncommon CNV.

Keywords: 9p21; Atherothrombotic stroke; CNV; Copy number variation; Genetic variation; Ischemic stroke.

MeSH terms

  • Adult
  • Aged
  • Asian People / ethnology
  • Asian People / genetics
  • Case-Control Studies
  • Chromosomes, Human, Pair 9 / genetics*
  • Cyclin-Dependent Kinase Inhibitor p15 / genetics
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • DNA Copy Number Variations / genetics*
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Purine-Nucleoside Phosphorylase / genetics
  • RNA, Long Noncoding / genetics
  • Retrospective Studies
  • Statistics, Nonparametric
  • Stroke / genetics*
  • Young Adult

Substances

  • CDKN2B antisense RNA, human
  • CDKN2B protein, human
  • Cyclin-Dependent Kinase Inhibitor p15
  • Cyclin-Dependent Kinase Inhibitor p16
  • RNA, Long Noncoding
  • Purine-Nucleoside Phosphorylase
  • 5'-methylthioadenosine phosphorylase