PPARα基因单体型与原发性高血压的关系

Genotype and haplotype analysis of peroxisome proliferators activated receptor α gene and the risk of essential hypertension

目的研究分析过氧化物酶体增殖物激活受体（PPAR）α基因3个多态位点（rs1800206、rs135539、rs4253778）与原发性高血压（EH）的关联。方法对820名研究对象（男270名，女550名）进行PPARα的基因多态性检测。对获得的数据进行单核苷酸多态性（SNP）和单体型关联分析。结果在显性模型中，携带162V等位基因（LV＋VV）和携带1C等位基因（AC＋CC）与EH的发生风险降低有关（OR=0．48，95％C10．40～0．64，P〈0．01；OR：0．75，95％C10．62～0．93，P=0．005）。在共显性模型中，162V杂合子（LV）和1c杂合子（ac）基因型和对应的野生型纯合子相比，可降低EH的发生风险（OR=0．48，95％C10．33～0．70，P〈0．01；OR=0．71，95％C10．56～0．88，P=0．003）；相反，携带7C纯合子（CC）基因型是野生纯合子高血压发生风险的3．16倍（95％CI1．86～6．94，P=0．002）。A—G—V和C—G—V单体型（rsl35539，rs4253778，rs1800206）会降低EH发生风险（OR=0．56，95％C10．33～0．82，P=0．027；OR=0．53，95％C10．30～0．84，P=0．033）。结论PPARα基因的单体型A-G-V和C—G—V可能是EH的保护因子，可降低EH的患病风险，PPARα基因是EH的重要易感基因。

Objective PPARα, which is expressed in the liver, heart, skeletal muscle, and kidney, regulates lipid and lipoprotein metabolism. The aim of this study was to investigate the association between the PPARα gene and essential hypertension （EH） using a haplotype-based cohort study in a Chinese-Han population. Methods 820 subjects （270 males, 550 females ） were genotyped for the three single-nucleotide polymorphisms used as genetic marker for the PPARα gene （ rs1800206, rs4253778 and rs135539）. Individual polymorpbism and haplotype data were available for analyses. Results In the dominant model, the presence of the G allele of rs1800206 and the C allele of rs135539 were at a decreased riskofEH （OR=0.48, 95%CI0.40-0.64, P〈0.01; 0R=0.75, 95%CI0.62-0.93, P〈0.01, respectively ）. A 3.16-fold increase （95 % C1 1.86 - 6. 94, P = 0. 002） in the risk of the development of EH was observed in homozygous genotype （ CC ） of rs4253778 compared to carriers of GG genotype （ co-dominant model）. The A-G-V and C-G-V haplotype （established by rs135539, rs4253778, rs1800206） was associated with a statistically significant decreased risk of EH （ OR = 0. 56, 95% CI 0. 33 - 0. 83, P = 0. 027 ; OR = 0. 53, 95 % CI 0. 30 - 0. 84, P = 0. 033, respectively）. Conclusion These results may help to clarify the role of PPARα gene in EH and the evaluation of its polymorphisms and haplotypes as being characterized as genetic decreased risk factors for EH.