Association Between HTRA1, GAS6 and IFNGR2 Gene Polymorphisms and Stroke Susceptibility in the Chinese Han Population

BACKGROUND: Stroke has a high disability rate, and 30% of stroke cases have an unknown cause. Accurate diagnosis and treatment of stroke requires consideration of several rare heritable and non-heritable factors. OBJECTIVE: This study aimed to evaluate the impacts of three genetic polymorphisms (rs369149111 in HTRA1, rs1803628 in GAS6 and rs9808753 in IFNGR2) on stroke susceptibility among the Chinese Han population. METHODS: Three single nucleotide polymorphisms (SNPs) from 623 stroke cases and 572 healthy controls were genotyped by the Agena MassARRAY platform. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression analysis to evaluate the associations of three SNPs with stroke susceptibility. Additionally, SNP-SNP interactions were analyzed by multifactor dimensionality reduction (MDR). RESULTS: As demonstrated by the overall analysis, rs9808753 in IFNGR2 (allele: OR = 1.25, 95% CI = 1.06–1.47, p = 0.007; homozygous: OR = 1.59, 95% CI = 1.14–2.23, p = 0.007; dominant: OR = 1.31, 95% CI = 1.02–1.67, p = 0.032; recessive: OR = 1.42, 95% CI = 1.05–1.91, p = 0.022; additive: OR = 1.26, 95% CI = 1.07–1.48, p = 0.007) was associated with an increased susceptibility to stroke. Besides, stratification analysis suggested that rs9808753 was associated with an increased risk of stroke in subgroup aged ≤ 64 years, males and drinkers (p < 0.05). And rs1803628 in GAS6 was significantly associated with an increased susceptibility to stroke in non-smokers (p < 0.05). CONCLUSION: A risk-increasing effect of IFNGR2 rs980875 on stroke was detected in this study, which further broadens the understanding of the relationship between genetic polymorphisms and stroke susceptibility.