ABSTRACT
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.
ABSTRACT
BACKGROUND: Stroke is a heterogeneous disease with multiple etiologies, placing a heavy burden on the world. Our purpose was to clarify the association between CASZ1 genetic variants and stroke risk in the Chinese population. METHODS: The Agena MassARRAY platform effectively genotyped three single nucleotide polymorphisms of CASZ1 in recruited 591 stroke patients and 553 healthy controls. Logistic regression genetic models were employed to evaluate the relationship between CASZ1 polymorphisms and stroke risk through odds ratios (ORs) and 95% confidence intervals (CIs). Then, the interaction between CASZ1 variants was detected by multifactor dimensionality reduction (MDR). Moreover, functional enrichment analyses of the CASZ1 gene were performed by Metascape. RESULTS: In this study, CASZ1 rs4845941 and rs778228 were significantly associated with an increased risk of stroke. In particular, the gender-stratified analysis also showed that rs778228 of CASZ1 had an association with higher stroke risk in females. The relationship between stroke susceptibility and the interaction models of rs4845941, rs778228, and rs17035539 forecasted by MDR were analyzed to improve the ability to predict stroke risk. Furthermore, we found CASZ1 and related genes might facilitate the occurrence of stroke. CONCLUSIONS: This study demonstrated that CASZ1 genetic variants (rs4845941 and rs778228) contribute to the occurrence of stroke in the Chinese population, and therefore has important implications for treating and preventing stroke.
ABSTRACT
INTRODUCTION: Ischemic stroke (IS) is an extremely complex disease caused by the combined action of multiple environmental and genetic factors. CYP1B1 is a member of the cytochrome P450 protein family, and it is an important human drug-metabolizing enzymes. We aimed to explore the association between CYP1B1 genetic variants and IS risk in Chinese Han population. METHODS: We recruited 1,150 participants to conduct a "case-control" study. The assessment of association between candidate CYP1B1 genetic variants (rs2855658, rs10916, rs162560, rs2567206) and IS risk was performed by SNPStats online software. In addition, false-positive report probability analysis was used to detect whether the positive findings were just chance or noteworthy observations. Finally, the interaction of candidate SNPs in IS risk was evaluated by multifactor dimensionality reduction. RESULTS: The results showed that CYP1B1-rs2855658 was a risk factor for IS among ≥60-year-old (dominant: p = 0.034; overdominant: p = 0.026), smoking (heterozygote: p = 0.009; dominant: p = 0.004; overdominant: p = 0.012; log-additive: p = 0.003), and drinking participants (homozygous: p = 0.036; dominant: p = 0.019; recessive: p = 0.012; log-additive: p = 0.006). CYP1B1-rs10916 also was a risk factor for IS patients among ≥60-year-old (heterozygote: p = 0.047; overdominant: p = 0.048), smoking (dominant: p = 0.050; overdominant: p = 0.049), and drinking participants (dominant: p = 0.019; overdominant: p = 0.038; log-additive: p = 0.013). CONCLUSION: CYP1B1-rs10916 and CYP1B1-rs2855658 can increase the IS risk in Chinese Han population who are ≥60 years old, smoking, or drinking alcohol.
