CDKN2B-AS1基因多态性与女性早发冠心病的相关性研究

Correlation Study Between CDKN2B-AS1 Gene Polymorphism and Female Premature Coronary Artery Disease Occurrence

目的:探讨CDKN2B-AS1基因位点rs4977574单核苷酸多态性(SNP)与女性早发冠心病的相关性。方法:采用病例对照研究,连续入选女性早发(<65岁发病)冠心病患者226例(病例组)和同期冠状动脉造影阴性、年龄匹配的女性患者79例(对照组),采用小测序法(SNa Pshot技术)检测CDKN2B-AS1基因位点rs4977574多态性,同时测定血浆中总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、甘油三酯(TG)、血尿酸(UA)、空腹血糖(FPG)及糖化血红蛋白(HbA1c)水平,评估rs4977574多态性与上述生物标志物的相关性。结果:与对照组相比,病例组血TG、UA、FPG、HbA1c水平明显升高(P<0.05),校正年龄、体重指数、相关病史及危险因素后,高HbA1c(HbA1c>6.2%)明显增加女性早发冠心病的发生风险(OR=3.35,95%CI:1.41~8.00,P=0.006);rs4977574基因型及等位基因频率在病例组和对照组中分布有显著差异(P<0.05),病例组等位基因G频率明显高于对照组(OR=1.24,95%CI:1.05~1.48,P=0.019)。进一步分析发现,rs4977574多态性与高HbA1c相关;与AA基因型受试者相比,(GG+GA)基因型受试者中高HbA1c的发生率明显增加(OR=2.08,95%CI:1.11~3.89,P=0.022)。结论:CDKN2B-AS1基因SNP位点rs4977574多态性与女性早发冠心病相关,并与高HbA1c相关。

Objective：To explore the relationship between single nucleotide polymorphism （SNP） rs4977574 in CDKN2B-AS1 gene and female premature coronary artery disease （pCAD） occurrence. Methods： Our research included 2 groups： pCAD group, n=226 consecutive patients≤65 years of age and Control group, n=79 subjects with matched age,without CAD. The genotype of CDKN2B-AS1 SNP rs4977574 was detected by SNaPshot. Blood levels of total cholesterol （TC）, low-density lipoprotein cholesterol （LDL-C）, high-density lipoprotein cholesterol （HDL-C）, triglycerides （TG）, uric acid （UA）, fasting plasma glucose （FPG） and glycosylated hemoglobin （HbA1c） were examined; relationships between rs4977574 polymorphism and the above parameters were assessed. Results： Compared to Control group, pCAD group had increased blood levels of TG, UA, FPG and HbA1c, P〈0.05. With adjusted age, body mass index （BMI）, relevant disease history and risk factors, elevated HbA1c （HbA1c〉6.2%） obviously increased the risk of female pCAD occurrence （OR=3.35, 95%CI 1.41-8.00, P=0.006）. The genotype and allele frequency of rs4977574 were different between pCAD group and Control group, P〈0.05. Compared to Control group, pCAD group had the higher frequency of G allele（OR=1.24, 95%CI 1.05-1.48, P=0.019）; further analysis found that rs4977574 polymorphism was related to high HbA1c. Compared to AA genotype, GG＋GA genotype had the increased incidence of high HbA1c（OR=2.08, 95%CI 1.11-3.89, P=0.022）. Conclusion： CDKN2B-AS1 SNP rs4977574 was related to female pCAD occurrence and it was also related to high HbA1c.