新疆哈萨克族人神经前体细胞表达发育调控蛋白4基因遗传变异的分布及其与代谢综合征的关系

摘要

Objective To investigate the gene polymorphism of neural precursor cell expressed developmentally down-regulated 4 (NEDD4) and its association with metabolic syndrome (MS) in Kazak ethnic group. Methods A total of 923 subjects (741 controls and 182 MS patients) from Kasak ethnic group were included in this case-control study based on epidemiologic survey. Genetic variations in NEDD4 were studied with gene sequencing, and Taqman- PCR was used to identify the genotypes of typical genetic variations. Results Twenty-seven genetic variations, including 6 missense mutations, were identified. The frequency distributions of five common single nucleotide polymorphisms (SNPs) did not differ between MS and controls (P＞0.05). After stratification by age, the SNP rs11550869 was associated with MS in Kazak patients aged ≥40 years (P=0.024 for both genotypee and dominant models). After adjusted for age and gender, the odd ratio was 1.604 (95％CI: 1.061-2.424, P=0.025) and 1.681 (95％CI: 1.073-2.633, P=0.023), respectively. Although the three genotypes of SNP rs11550869 polymorphism did not differ in frequency distribution or phenotypes (P＞0.05), the values or levels of waist circumference, body mass index, fasting blood glucose, 2-hour postprandial glucose and HOMA index tended to be increasing from GG to GC and to CC. Moreover, haplotype 5 (A-A-T-A-C, containing the C allele of rs11550869) appeared to be more common in MS subjects as comparea to controls (Permutation test, P=0.059). Conclusion The SNP rs11550869 of NEDD4 gene may be associated with MS in Kazak population aged 40 years or older, although this finding warrants validation in further studies.%目的 探讨神经前体细胞表达发育调控蛋白4(NEDD4)基因多态与哈萨克族人代谢综合征(MS)的关系。方法 采取以流行病学调查为基础的病例对照研究，选择923例哈萨克族人(741例对照和182例MS)为研究对象。测序筛查NEDD4基因变异，用Taqman-PCR行代表性变异的基因型鉴定。结果测序发现27个变异，包括6个错义突变。5个常见变异在MS病例和对照组间频率分布差异无统计学意义(P＞0.05)，但rs11550869变异与≥40岁哈萨克族人的MS相关(基因型和显性模型中均P=0.024)，控制年龄和性别后，0R值1.604 (95％CI 1.061～2.424,P=0.025)、1.681 (95％CI 1.073～2.633，P=0.023)；rs11550869变异不同基因型间MS组分数量性状比较差异无统计学意义(P＞0.05)，但3种基因型间(GG＜GC＜CC)腹围、体质量指数、空腹血糖、餐后2h血糖、胰岛素抵抗指数均有逐渐增高趋势；且常见单倍型H5（A-A-T-A-C，包含rs11550869位点C等位基因）频率在病例组较对照组高(P=0.059)。结论 NEDD4基因rs11550869变异位点与新疆哈萨克族40岁以上人群MS可能相关，该结果需进一步验证。