社区人群亚甲基四氢叶酸还原酶基因多态性与颅内动脉粥样硬化性狭窄的相关性研究

Correlation of MTHFR genetic polymorphism to intracranial atherosclerotic stenosis in community population

摘要:

目的：研究社区人群亚甲基四氢叶酸还原酶（methylenetetra-hydrofolate reductase，MTHFR）基因型的分布差异，探讨社区人群中MTHFR c677t基因突变与颅内动脉粥样硬化性狭窄（intracranial atherosclerotic stenosis，ICAS）是否关联。方法：利用便利抽样方法，收集2016年1月至2017年5月在重庆医科大学附属第一医院健康体检部体检的汉族人群698例，记录其既往病史、生理、生化指标等病史资料。采用Sanger测序法鉴定目标人群MTHFR c677t位基因型，经颅多普勒（transcranial Doppler，TCD）检查ICAS。采用卡方检验分析组间频率型数据差异有无统计学意义；多因素logistic回归分析ICAS的相关影响因素。结果：MTHFR c677t基因型频率分布以及两基因型联合比较（C/T +T/T与C/C）在有无ICAS两组间差异具有统计学意义（ χ2=13.347，P=0.000）。基因型两两比较中，T/T与C/C（ χ2=12.064，P=0.000）以及C/T与C/C（ χ2=10.414，P=0.000）比较差异均具有统计学意义，ICAS组的T等位基因频率明显高于非颅内动脉粥样硬化性狭窄（non-intracranial atherosclerotic stenosis，NICAS）组。多因素logistic回归分析结果显示：MTHFR c677t T/T（OR=2.34，95%CI=1.363~4.016，P=0.002）和C/T（OR=2.34，95%CI=1.363~4.016，P=0.002）基因型可能是ICAS的遗传易感基因。结论：中国社区人群中存在MTHFR c677t基因突变。MTHFR c677t基因多态性与颅内动脉粥样硬化性狭窄风险增加有关。

Abstract:

Objective：To investigate the distribution of methylenetetra-hydrofolate reductase（MTHFR） genotypes in community popu－lation，and explore the relationship between MTHFR c677t polymorphisms and intracranial atherosclerotic stenosis. Methods：Six hundred and ninety-eight adult Han people were selected from the people undergoing physical examination in the First Affiliated Hospital of Chongqing Medical University from January 2016 to May 2017 by convenience sampling. Their past medical history，and physiological and biochemical indicators were recorded. The MTHFR c677 genotypes of target group were detected by polymerase chain reaction-restriction fragment length polymorphism（PCR-RFLP），and the intracranial atherosclerotic stenosis（ICAS） by transcranial Doppler（TCD）. The results were analyzed by Chi-square test for statistical difference and multiple factor logistic regressions for the correlated influencing factors of ICAS. Results：There was significant distribution difference between the ICAS and NICAS group of allele frequencies（C/T + T/T and C/C， χ2=13.347，P=0.000）. The differences between the genotype groups are also significant（T/T and C/C， χ2=12.064，P=0.001；and C/T and C/C， χ2=10.414，P=0.000）. The frequencies of T allele in community population with ICAS were obviously higher than those of the control. The multiple factor logistic regression analysis showed that T/T（OR=2.34，95%CI=1.363 to 4.016，P=0.002） genotype and C/T（OR=2.34，95%CI=1.363 to 4.016，P=0.002） genotype were probably the independent risk factor for intracranial atherosclerotic stenosis. Conclusion：There is a genetic polymorphism of MTHFR c677t in community population in China，which is correlated with the increased risk of ICAS.