title: Linkage and association between interleukin-6 gene polymorphisms and ischemic stroke: a family-based study in the northern Chinese Han population.
abstract: BACKGROUND
  Numerous genetic risk factors of ischemic stroke (IS) have been reported from both candidate gene and genome-wide strategies with inconsistent results. The objective of this study was to confirm the relationship between 10 previously identified single-nucleotide polymorphisms (SNPs) and IS in the Chinese population.
  
  
  METHODS
  A family-based study was conducted in a rural area of Beijing, with a total of 227 IS families with 622 participants recruited. Both linkage and association analyses were performed, with all the sibling pairs derived from the 227 families analyzed using the sib-pair test of model-free linkage to assess linkage between SNPs and IS, with association analyses including a family-based association test (FBAT) and generalized estimating equations (GEE).
  
  
  RESULTS
  Nonparametric linkage analysis revealed that the rs1800796 polymorphism in the interleukin-6 (IL-6) gene is significantly linked to the small arterial occlusion (SAO) subtype (p=0.022), while the rs7193343 polymorphism in the ZFHX3 gene is linked to IS (p=0.002) under the dominant model. Significant allelic associations were identified between the G allele of rs1800796 and IS (p=0.042) and the SAO subtype (p=0.025) in the FBAT. The GEE method revealed that the G allele of rs1800796 increased IS risk by 1.55-fold (95% 95% confidence interval [CI]: 1.01, 2.37; p=0.043) and 2.43-fold (95% CI: 1.32, 4.45; p=0.004) in the SAO subtype in the dominant model, which correlated with the significant associations detected in the FBAT.
  
  
  CONCLUSIONS
  In this study, we confirmed that the SNP of rs1800796 in the IL-6 gene is related to IS and the SAO subtype using different statistical approaches. These findings could contribute to identifying individuals with a high IS risk.
authors.affiliation: 1 Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center , Beijing, People's Republic of China .
authors.forename: Xue-Yin
authors.initials: XY
authors.lastname: Wang
authors.forename: Jin-Wei
authors.initials: JW
authors.lastname: Wang
authors.forename: Xun
authors.initials: X
authors.lastname: Tang
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.forename: Da-Fang
authors.initials: DF
authors.lastname: Chen
authors.forename: Yi-Qun
authors.initials: YQ
authors.lastname: Wu
authors.forename: Xue-Ying
authors.initials: XY
authors.lastname: Qin
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.forename: Kuo
authors.initials: K
authors.lastname: Liu
authors.forename: Kai
authors.initials: K
authors.lastname: Fang
authors.forename: Yong-Hua
authors.initials: YH
authors.lastname: Hu
mesh_terms: D000328:Adult; D000483:Alleles; D044466:Asian People; D002545:Brain Ischemia / Q000235:genetics*; D002681:China; D005190:Family; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D020521:Stroke / Q000235:genetics*
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6