中国人早发2型糖尿病PAX4基因多态性及临床表型特点

PAX4 gene polymorphism and clinical characteristics of early-onset type 2 diabetes in Chinese

目的研究早发2型糖尿病患者成对盒4(PAX4)基因外显子3和9的多态及临床表型特点。方法以96例早发2型糖尿病患者(早发糖尿病组,n=96)和100名口服葡萄糖耐量试验正常者(对照组)作为研究对象。采用聚合酶链反应(PCR)直接测序法对两组人群PAX4基因外显子3和9的基因多态进行筛查,对基因型、等位基因分布频率以及临床表型变量进行统计学分析。结果两组人群检出位于PAX4基因外显子9的His321Pro(A→C)多态,外显子3未检出多态。早发糖尿病组PAX4基因外显子9 His321Pro(A→C)多态CC基因型和C等位基因分布频率(16.7%和41.1%)高于对照组(11.0%和34.0%),但差异无统计学意义(P>0.05);本研究对照人群PAX4基因外显子9的His321Pro(A→C)多态CC基因型及C等位基因分布频率显著低于瑞士、德国、芬兰和匈牙利相关研究的正常对照人群(P<0.001)。早发糖尿病组与对照组PAX4基因外显子9His321Pro(A→C)多态纯合子CC基因型携带者空腹C肽水平显著低于AA和AC基因型携带者(P<0.05)。结论 PAX4基因多态性可能不是中国人早发2型糖尿病的遗传易感标志。PAX4基因外显子9的His321Pro(A→C)多态可能与空腹胰岛素分泌受损有关。

Objective To screen the polymorphism in exon 3 and 9 of paired box4(PAX4) gene and investigate the clinical characteristics of early-onset type 2 diabetes in Chinese.Methods Ninety-six patients with early-onset type 2 diabetes(early-onset diabetes group) and 100 people with normal results in oral glucose tolerance test(control group) were enrolled.PCR-direct sequencing was employed to detect polymorphism in exon 3 and 9 of PAX4 gene in two groups,and genotypic and allelic frequencies and clinical characteristics were statistically analysed.Results His321Pro(A→C)polymorphism in exon 9 of PAX4 gene was detected in both groups,while no polymorphism was found in exon 3 of the gene.In comparison with control group,higher frequencies of CC genotype and C allele of His321Pro(A→C) polymorphism in exon 9 of PAX4 gene were detected in early-onset diabetes group,while there was no significant difference between groups(16.7% vs 11.0% and 41.1% vs 34.0%,P>0.05 for both).The frequencies of CC genotype and C allele of His321Pro(A→C) polymorphism in exon 9 of PAX4 gene in controls of this study were significantly lower than those in studies of Switzerland,Germany,Finland and Hungary(P<0.001).The fasting C peptide(FCP) levels of homozygous CC genotype carriers were significantly lower than those of AA and AC genotype carriers with His321Pro(A→C) polymorphism in exon 9 of PAX4 gene in early-onset diabetes group and control group(P<0.05).Conclusion PAX4 gene polymorphism may not be the genetic susceptibility marker associated with the development of early-onset type 2 diabetes in Chinese.His321Pro(A→C)polymorphism in exon 9 of PAX4 gene may be associate with impaired fasting insulin secretion.