新疆哈萨克族转化生长因子β1基因多态性及其血浆水平与原发性高血压的关系

摘要

目的 研究新疆哈萨克族原发性高血压(essential hypertension,EH)患者转化生长因子β1(transforming growth factor-β1,TGF-β1)+869T/C、+915G/C基因多态性及血浆水平与EH的关系.方法 采用聚合酶链反应-限制性片段长度多态性和基因测序对新疆哈萨克族365名EH患者及435名正常对照组进行基因分型,用双抗体夹心法测量TGF-β1血浆浓度.结果 +915G/C位点基因型GG、GC及等位基因G、C频率依次为97.9%、2.1%、98.77%、1.23%,EH组与对照组差异无统计学意义(P＞0.05);+869T/C位点基因型TT、TC、CC及等位基因T、C在对照组中频率依次为25.97%、46.67%、27.36%、49.3%、50.7%,CC基因型及C等位基因频率在EH组中高于对照组(41.60%vs.27.36%、62.2%vs.50.7%),差异有统计学意义(P＜0.05),C等位基因携带者EH患病风险高于T等位基因携带者(OR=1.6O,P=0.00).+869T/C与+915G/C存在连锁不平衡,其形成的单倍型C-G在EH组中频率高于对照组(61.6%vs.49.8%,P＜0.05).+869T/C及+915G/C基因型、等位基因在EH组和对照组中TGF-β1血浆水平差异无统计学意义(P＞0.05).结论 新疆哈萨克族TGFβ1+915G/C基因变异频率很低,且不存在纯合变异,+869位点C等位基因可能是哈萨克族EH的遗传易感基因,+869T/C与+915G/C多态性位点存在连锁不平衡,两者构成的单倍型C-G是EH危险性因素.%Objective To investigate the association of the transforming growth factor-β1 (TGF-β1)gene polymorphisms and blood TGF-β1 level with essential hypertension (EH) in Kazakh Chinese. Methods The polymorphisms of TGF-β1 gene in 354 Kazakh EH patients and 435 healthy controls were detected with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing.The blood level of TGF-β1 was quantified using specific sandwich ELISA. Results The frequencies of genotypes GG, GC and alleles G and C of +915G/C in Xinjiang Kazakh were 97.9%, 2.1% and 98. 77%,1.23%, respectively. No significantly difference was found between EH patients and controls (P＞0.05).The frequencies of genotypes TT, TC, CC and alleles T and C of +869T/C in controls was 25.97%,46.67%, 27.36%, 49. 3% and 50.7%, respectively, the CC genotype or C allele in EH patients had significantly higher frequencies than controls[41.60% vs. 27.36%, and 62.2% vs. 50.7%, respectively (P＜0.05)]. It was also shown that TGF-β1 +869 C allele carriers had significantly increased risk of EH compared with T allele carriers (OR=1.60,P= 0.00). There was linkage disequilibrium (LD) between the two polymorphisms. The frequency of haplotype C-G in the EH group was significantly higher than that in controls (61.6% vs. 49.8%, P＜ 0.05). There were no differences in TGF-β1 level among different genotypes or alleles in both + 869T/C and + 915G/C loci (P＞ 0.05). Conclusion The frequency of +915G/C variation of the TGF-β1 gene was very low in Kazakh and there was no homozygous variation.The + 869 C allele was likely the genetic susceptibility factor for EH in the population. There was linkage disequilibrium in the polymorphisms of + 869T/C and +915G/C. Haplotype C-G was the risk factor of EH.