转化生长因子β3基因三个单核苷酸多态性与中国人群高血压病未见相关

No association between 3 polymorphisms of transforming growth factor β3 gene and essential hypertension in Chinese

目的 探讨转化生长因子β3 (TGF β3 )基因单核苷酸多态性 (singlenucleotidepolymorphisms, SNP)与中国人高血压病(EH)的关系。方法 通过直接测序法筛选位于TGF β3基因启动子、编码区和部分内含子中SNP,作为关联研究的遗传标记。采用病例 对照研究,利用限制性片段长度多态性 (RFLP)及等位基因专一PCR法,在 396例EH患者及 214例正常对照人群中,进行TGF β3基因编码区Thr63Asn、内含子区SS5608219、SS5608220三个多态性基因型检测,比较病例与对照组间基因型分布及基因频率的差异。结果 TGF β3基因测序总长度 5457bp,共发现 7个SNP,位于内含子区 5个、编码区和 3′非翻译区各 1个。其中 2个为新发现的SNP,包括 1个位于编码区能引起氨基酸改变的Thr63Asn多态性。在病例 对照研究中,Thr63Asn、SS5608219和SS5608220三个多态性的基因型分布和等位基因频率,在EH组与正常对照组之间差异无统计学意义 (P>0 05 )。结论 在中国人TGF β3基因中,新发现 2个SNP,其中 1个位于外显子 1第 63密码子(A→C),可引起组氨酸替代天门冬酰胺。但在关联研究中,未发现TGF β3基因的三个SNP与中国汉族人群EH有关。

Objective To investigate possible association between the single nucleotide polymorphisms (SNPs) of transforming growth factorβ3 ( TGF β3 ) gene and essential hypertension (EH) in Chinese. Methods The promoter region, exons, as well as part of the introns of TGF β3 gene were sequenced by a fluorescent labeling automatic sequencing method to detect and characterize the SNPs in 24 DNA samples from a Chinese population. Then we conducted a case control study using 396 patients with hypertension (case) and 214 nomortensive subjects (control). The three SNPs including Thr63Asn, SS5608219 and SS5608220 were genotyped by PCR RFLP or real time allele specific PCR in subjects studied. Results Seven SNPs in the exons, introns and 3′untranslated region (3′UTR) of TGF β3 gene were identified. Among them, 2 SNPs were found to be novel genetic variants and one of the two located in the exon 1 and produced substitution of amino acid. However, no differences were found between hypertensives and nomortensives in genotype distribution and allele frequency of SS5608219, Thr63Asn or SS5608220 polymorphisms. Conclusions Two novel SNPs of TGF β3 gene were identified in Chinese. One of them produces a threonine to asparagines substitution in codon 63 (Thr63Asn). But no association was found between TGF β3 gene polymorphisms and EH in Chinese .