Ⅰ型血管紧张素Ⅱ受体相关蛋白基因多态性与高血压的相关性研究

Association Study of ARAP1 Polymorphisms and Hypertension

目的探讨Ⅰ型血管紧张素Ⅱ受体相关蛋白(AT1 receptor-associated protein,ARAP1)基因的常见多态rs2787594,rs11795066,rs13298677和rs4837129与高血压之间的关联关系。方法选择503例高血压病例和490例年龄、性别相匹配的健康对照。所有个体均为中国北方汉族人。采用多聚酶链式反应一限制性片段长度多态性(PCR-RFLP)方法进行基因型鉴定。结果校正协变量前后,所有SNPs均与高血压无关联。单体型分析也没有发现与高血压关联的单体型。应用线性回归模型校正年龄和性别的作用,比较不同基因型个体的体重指数(BMI)、血糖和血脂水平的差异。rs2787594多态CC纯合子与升高的血糖水平显著关联(CC/TT+TC,6.09+0.24vs.5.54+0.08mmol/L,P=0.0296)。在显性模型中,rs11795066 A等位基因显著升高了个体的BMI水平(GA+AA/GG,24.81±0.29vs.24.07±0.19kg/m2,P=0.0331)。rs13298677多态G等位基因与较低的BMI水平(GG/GA+AA,22.84±0.74vs.24.37±0.16kg/m2,P=0.0438)以及TG水平(GG+GA/AA,1.34±0.06vs.1.50±0.05mmol/L,P=0.0413)显著关联。结论 ARAP1基因4个SNPs与高血压无显著关联,但与对照个体的血脂、血糖和BMI关联,该基因变异可能影响了我国人群血脂、血糖的代谢。

Objective To investigate the relationship of the polymorphisms （rs2787594, rs11795066, rs13298677 and rs4837129） of ARAP1 gene with essential hypertension. Methods Four SNPs of ARAP1 gene were genotyped among 503 cases with hypertension and 490 controls using the RFLP-PCR methods, and the genotype and allele frequencies of all SNPs of ARAP1 gene in all subjects were analyzed. Results Before and after adjustment for covariate, all SNPs were not associated with essential hypertension. Haplotype analysis indicated that there was no haplotype associated with essential hypertension. A general linear model was used to compare lipid quantity traits among genotypic groups adjusting for covariates including age and gender. Homozygosity CC for rs2787594 had the increased blood glucose level （CC/TT＋TC, 6.09＋0.24 vs. 5.54＋0.08 mmol/L, P=0.0296）. The rs11795066 A carriers had an increased BMI compared with subjects with rs2787594 GG genotype （GA＋AA/ GG, 24.81±0.29 vs. 24.07±0.19 kg/m2, P=0.0331）. The rs13298677 G allele was associated with the decreased BMI （GG/GA＋AA, 22.84±0.74 vs. 24.37±0.16 kg/m2, P=0.0438） and TG levels （GG＋GA/AA, 1.34±0.06 vs. 1.50±0.05 mmol/L, P =0.0413）. Conclusion Four SNPs of ARAP1 gene were not associated with essential hypertension. However, ARAP1 gene variants were associated with the glucose and lipid phenotypes among Chinese normaltensive subjects, which suggested these variants may be influence the metabolism of glucose and lipids.