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.