肾上腺髓质素基因多态与中国人血脂水平的关系

Association of Adrenomedullin Gene Polymorphisms with Blood Lipid Levels in Chinese Population

目的本研究旨在探索肾上腺髓质素(ADM)基因单核苷酸多态(SNP)与中国汉族人群血脂水平的关联关系。方法研究纳入2337例无高血压、糖尿病、心血管病和恶性肿瘤等病史的个体,选择ADM基因的3个标签SNPs进行基因分型。采用广义线性模型调整年龄、性别和体重指数(BMI),分析多态与血脂水平的关系。结果 ADM基因的3个标签SNPs均与血脂水平呈线性关联关系。随着携带危险等位基因(rs4399321A、rs4910118C和rs7944706A)数目的增加,个体总胆固醇水平(标准误)逐渐增高,分别为189.1(1.7)mg/dl、190.9(1.2)mg/dl和195.4(1.6)mg/dl(P趋势=0.004),低密度脂蛋白胆固醇水平也逐渐增高,分别为113.7(1.5)mg/dl、114.4(1.1)mg/dl和119.0(1.4)mg/dl(P趋势=0.006)。结论 ADM基因常见多态与中国人群血脂水平关联,提示ADM基因可能参与调节脂质代谢,从而影响我国人群的血脂水平。

Objective Dyslipidemia is an important risk factor of cardiovascular disease. The high heritability of circulating lipid level is well established, whereas, the genetic structure of lipid metabolism has not been fully understood. The present study was aimed to examine the associations between genetic variants of the adrenomedullin（ADM） gene and lipid levels in Chinese Han population. Methods A total of 2337 Chinese adults without history of hypertension, diabetes, cardiovascular diseases or cancer were recruited in the present study. Three tagging single nucleotide polymorphisms（SNPs） based on Hap Map CHB data were selected and genotyped. Lipid levels were compared by general linear model after adjusted for multiple covariates, including age, gender and body mass index. Results There were significant associations between serum lipids and 3 tagging SNPs（rs4399321, rs4910118 and rs7944706） of the ADM gene. Concentrations of total cholesterol and low density lipoprotein cholesterol were linearly associated with the number of risk alleles. Among participants with 1-2, 3-4 and 5-6 risk alleles, serum concentration of total cholesterol was 189.1（1.7） mg/dl, 190.9（1.2） mg/dl and 195.4（1.6） mg/dl（P for trend is 0.004）, respectively, serum concentration of low density lipoprotein cholesterol was 113.7（1.5） mg/dl, 114.4（1.1） mg/dl and 119.0（1.4） mg/dl（P for trend is 0.006）, respectively. Conclusion Genetic variations of the ADM gene were associated with blood lipid concentrations in Chinese population. These findings suggest that the ADM gene may involve in lipid metabolism and influence blood lipid levels in Chinese. In addition, replications in other populations and further functional studies are required to confirm and interpret the association of ADM with lipids.