三个候选基因多态性与高血压病关联的研究

Single nucleotide polymorphisms of three candidate genes in essential hypertension

目的探讨转化生长因子β1(TGFβ1)T869C、醛固酮合成酶(CYP11B2)-344T/C和α内收蛋白Gly460Trp3个单核苷酸多态性(SNPs)与原发性高血压(EH)的关系。方法采用限制性片段长度多态性和突变基因分离PCR法,在396例EH患者和214例正常人中分析T869C、-344T/C和Gly460Trp多态性的基因型分布。结果在单基因研究中,女性EH患者与对照组比较,TGFβ1T869C基因型和等位基因频率差异有统计学意义(P值分别=0.017,0.014);与T等位基因携带者相比,CC纯合子EH患病率差异有统计学意义(OR=2.97,95%CI1.38～6.32,P=0.004);而男性则两组间T869C基因型分布和等位基因频率差异无统计学意义(P>0.05)。采用多基因联合分析,TGFβ1CC纯合子中,CYP11B2TT纯合子EH患病率高于C等位基因携带者(OR=1.99,95%CI1.01～3.74,P=0.03)。结论TGFβ1T869C多态性可能与中国汉族女性EH相关;在EH人群中,TGFβ1T869C和CYP11B2-344T/C多态性可能有协同作用。

Objective To explore the association of single nucleotide polymorphisms （SNPs） of three candidate genes, including T869C of transforming growth factor β1 （TGF-β1）, -344T/C of aldosterone synthase （CYP1182 ） and Gly460Trp of α-Adducin with essential hypertension in Chinese Han population. Methods Three hundred ninety six hypertensive patients and 214 normotensive subjects were genotyped for T869C, -344T/C and Gly460Trp polymorphisms with polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） and mutngenically separated PCR （MS-PCR）, respectively. Results In single-gene analysis, no association was observed between either CYPlIB2 -344T/C or α-Adducin Gly460Trp polymorphism and essential hypertension. For female, there were significant difference in genotype distribution and allele frequency of T869C polymorphism （P 〈 0. 02）, as compared with subjects with T allele. CC homozygosity had a higher relative risk of hypertension （ OR = 2. 97, 95% CI, 1.38 to 6. 32, P =0. 004）, whereas we failed to detect any association between T869C polymorphism and essential hypertension in male. In multiple-gene analysis, the incidence of hypertension was higher in CYP1182 TT homozTgosity than in other CYP1182 genotypes （OR = 1.99, 95%CI, 1.01 to 3.74, P =0.03） in the presence of TGF-β1 CC genotype. Condusions Our results indicated that T869C polymorphism of TGF-β1 gene might be associated with essential hypertension in female, furthermore, the TGF-β1 T869C and CYP1182-344T/C polymorphisms appeared to interact in hypertensive population.