中国汉族人群GH1基因启动子区单体型及与身高的关系

Haplotyping of GH1 Gene Proximal to Promoter Region and the Association with Adult Height in Chinese Han Population

目的研究中国汉族人群GH1基因启动子区域的单核苷酸多态性及其在中国汉族人群中的分布规律,建立其单体型分析方法并探索与成年人身高间的关系,为今后个体身高特征推测研究奠定基础。方法采用直接测序法进行SNP检测,获得其分型数据;采用等位位点特异性PCR方法和基于人群的单体型推断方法分别进行单体型分析,并采用Haplo.stats软件构建单体型与身高的广义线性模型。结果 GH1基因启动子区域含有多个SNP位点,在前人研究的基础上发现了-261、-250、+20三个新SNP位点;找到-278、-57、-6三个标签SNP位点,以最常见的单体型GTA为参照,TTA、GGG、TTG携带者的身高更矮(P<0.05),差异具有统计学意义。结论基于人群的单体型推断方法是一种比较准确可行的方法,可以在后续的研究中单独使用,不需要再进行复杂费时的等位位点特异性PCR操作;GH1基因启动子区域在中国汉族人群中表现出高度多态性,并存在一定的人种差异;GH1基因启动子区域的序列及单体型与身高存在一定的关系。

Objective The aim of this study is to investigate the single nucleotide polymorphisms （SNPs） located at the GH1 gene proximal to promoter region in Chinese Han population, and to explore its haplotype association with adult height. Methods SNP typing was performed by direct DNA sequencing in a control Chinese population of 109 unrelated male adults. By using both allele-specific PCR and the Haploview software, the haplotypes on the basis of the SNPs were obtained. Haplo.stats software was employed to analyze the association between haplotype and adult height. Results 69 samples were successfully genotyped with 34 samples bearing at least two polymorphic sites. 13 SNPs were found in the GH1 gene proximal to promoter region in Chinese Han population, and three of them located at sites of-261, -250 and ＋20, were discovered for the first time. The same results of haplotypes were obtained by using both allele-specific PCR and Haploview software. Three tag SNPs were found at -278, -57 and -6 sites. Seven haplotypes were detected （GGA, GGG, GTA, TGA, TGG, TTA, TTG）, and statistical results indicated that people with TTA, GGG and TTG haplotypes were significantly shorter in height than those with GTA, the most common type in Chinese Han population （P〈0.05）. Conclusions Computation of haplotypes on SNPs based on the population data is relatively correct and can be applied to the haplotype analysis independently. The GH1 gene proximal to promoter region in Chinese Han population is highly polymorphic and differs among races, and its haplotypes may contribute to the human height. Taken together, this paper provides essential data on the associations between human height and GH1 proximal haplotypes.