KCNJ11 rs5210位点多态性与非酒精性脂肪性肝病及冠心病的遗传易感性分析

Abstract

目的 在青岛地区汉族人群中，研究内向整流钾通道蛋白J亚单位11号成员(KCNJ11)基因rs5210位点多态性与非酒精性脂肪性肝病(NAFLD)及冠心病(CAD)的相关性。 方法 随机纳入2018年12月—2019年9月就诊于青岛市市立医院的246例NAFLD患者为NAFLD组，201例CAD患者为CAD组，116例NAFLD合并CAD患者为合并组，342例健康对照人群为对照组。采集空腹静脉血进行生化检测。提取全血基因组DNA，采用PCR的方法进行KCNJ11 rs5210基因型测定。应用χ²检验分析KCNJ11 rs5210基因频率分布是否符合Hardy-Weinberg平衡法则，以确定检验样本是否具有群体代表性。应用χ²检验分析各组之间性别、基因型及等位基因频率的差异性。符合正态分布的计量资料多组间比较采用单因素方差分析，进一步两两比较采用LSD-t检验；不符合正态分布计量资料多组间比较采用Kruskal-Wallis H检验，两两比较采用Bonferroni法。应用非条件logistic回归模型计算比值比(OR)及95%可信区间。 结果 经测序发现KCNJ11 rs5210具有AA、GA、GG 3种基因型。对照组、NAFLD组、CAD组及合并组之间进行比较rs5210位点等位基因频率和基因型分布均无统计学差异(P值均＞0.05)。经校正年龄、性别、BMI，差异亦无统计学意义(P值均＞0.05)。全部受试人群中，携带AA基因型受试者ALP水平高于GA基因型(P=0.048)；在NAFLD组中，与携带AA基因型受试者相比，GA基因型携带者具有更高的BMI、TBil水平(P值分别为0.042、0.002)。非条件logistic回归分析表明，BMI升高与NAFLD患病风险相关(OR=1.35，P＜0.01)，HDL降低可提示NAFLD患病风险增加(OR=0.33，P＜0.01)；FPG升高、HDL降低可提示CAD(OR=1.51，P＜0.01;OR=0.11，P＜0.01)、NAFLD+CAD(OR=1.46，P＜0.01;OR=0.06，P＜0.01)患病风险增加。 结论 青岛地区汉族人群中KCNJ11 rs5210多态性与NAFLD及CAD的发病风险无明显相关性。

Alternate abstract:

Objective To investigate the association of KCNJ11 rs5210 single nucleotide polymorphism with nonalcoholic fatty liver disease (NAFLD) and coronary artery disease (CAD) in the Chinese Han population in Qingdao, China. Methods A total of 246 patients with NAFLD who attended Qingdao Municipal Hospital from December 2018 to September 2019 were enrolled as NAFLD group, 201 patients with CAD were enrolled as CAD group, and 116 patients with NAFLD and CAD were enrolled as NAFLD+CAD group; 342 healthy individuals were enrolled as control group. Fasting venous blood samples were collected for biochemical analysis. Whole blood genomic DNA was extracted, and PCR was used to determine KCNJ11 rs5210 genotype. The chi-square test was used to analyze whether the distribution of KCNJ11 rs5210 gene frequencies met the Hardy-Weinberg equilibrium, in order to determine whether the tested samples could represent the population. The chi-square test was used to analyze the differences in sex and genotype/allele frequency between groups. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups; the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups, and the Bonferroni method was used for further comparison between two groups. The unconditional logistic regression model was used to calculate odds ratio (OR) and 95% confidence interval. Results Three genotypes (AA, GA, and GG) of KCNJ11 rs5210 were found by gene sequencing. There were no significant differences in rs5210 allele frequency and genotype distribution between the control group, the NAFLD group, the CAD group, and the NAFLD+CAD group (all P > 0.05), and there were still no significant differences after adjustment for sex, age, and body mass index (BMI) (all P > 0.05). For all subjects, the subjects with AA genotype had a higher level of alkaline phosphatase than those with GA genotype (P=0.048); in the NAFLD group, the patients with GA genotype had significantly higher BMI and total bilirubin than those with AA genotype (P=0.042 and 0.002). The unconditional logistic regression analysis showed that elevated BMI was associated with the risk of NAFLD (OR=1.35, P < 0.01), while decreased high-density lipoprotein (HDL) might indicate an increase in the risk of NAFLD (OR=0.33, P < 0.01); elevated fasting plasma glucose and decreased HDL might indicate an increase in the risk of CAD (OR=1.51 and 0.11, both P < 0.01) and NAFLD with CAD (OR=1.46 and 0.06, both P < 0.01). Conclusion There is no significant association between KCNJ11 rs5210 polymorphism and the risk of NAFLD and CAD in the Chinese Han population in Qingdao.