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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 the relationship between single nucleotide polymorphism (TGFβ3) gene polymorphism of transforming growth factor β3 (TGFβ3) and Chinese hypertension (EH). Methods The SNPs located in the promoter, coding region and partial intron of TGFβ3 gene were screened by direct sequencing as a genetic marker for association study. Using case-control study, restriction fragment length polymorphism (RFLP) and allele-specific PCR were used to detect Thr63Asn and intron regions of TGFβ3 coding region in 396 EH patients and 214 normal control subjects SS5608219, SS5608220 genotypes of three polymorphisms were detected, genotype distribution and frequency differences between cases and control groups were compared. Results The total length of TGFβ3 gene was 5457bp. Seven SNPs were found, including 5 intron regions and 1 in coding and 3 ’untranslated regions. Two of them are newly discovered SNPs, including one Thr63Asn polymorphism that causes amino acid changes in the coding region. In the case-control study, the genotypes and allele frequencies of Thr63Asn, SS5608219 and SS5608220 were not significantly different between EH group and normal control group (P> 0.05). Conclusions Two new SNPs were found in Chinese TGFβ3 gene. One of them was located at codon 63 of exon 1 (A → C), which caused histidine to replace asparagine. However, in the association study, we did not find that the three SNPs of TGFβ3 were associated with EH in Chinese Han population.