Zhou Min, Zhang Ying, Zhang Dongmei, Lin Jian, Wang Jianping, Zhou Haifeng, Zhou Zhiguang
Diabetic Center, Institute of Metabolism and Endocrinology, Central South University, Changsha 410011, China.
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2010 Mar;35(3):215-21. doi: 10.3969/j.issn.1672-7347.2010.03.005.
To investigate PAX4 gene polymorphism and its association with islet autoantibody-negative patients with ketosis-prone diabetes in Chinese Han population.
We screened the variation of exon 3 and 9 within PAX4 gene by denaturing high performance liquid chromatography(DHPLC) in 112 non-diabetes control subjects (NC group) and 141 patients with ketosis-prone diabetes (KPD group), who were both negative for glutamic acid decarboxylase antibody (GAD-Ab) as well as protein tyrosine phosphatase antibody (IA-2Ab). The sequences of abnormal peaks were analyzed by DNA-sequencing. The A1168C single nucleotide polymorphism in PAX4 gene was genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 308 non-diabetic control subjects and 141 KPD patients.
No variation was discovered in PAX4 gene exon 3 both in the patients and in the controls. There was a single nucleotide polymorphism locus A1168C in the PAX4 gene exon 9, which induced missence mutation P321H (rs712701). No significant difference was observed in the genotype and allele frequencies of A1168C polymorphism between KPD patients and control subjects (P=0.532, 0.426). The difference was detected in the CC genotype and C allele frequencies in the KPD group when patients were stratified by gender (P=0.009,0.028). According to age at diagnosis, the difference was observed in the CC genotype and C allele frequencies between <20 years old and > or = 20 years old in the KPD group (P=0.034,0.032). The level of FCP in the CC genotype group was significantly higher than that of FCP in AA genotype group (P=0.005).
A1168C polymorphism in PAX4 gene may not play an essential role in the genetic susceptibility of the islet autoantibody-negative KPD in Chinese Han population. However, A1168C variation may contribute to the predisposition to the male or < 20 years old patients with islet autoantibody-negative KPD.
研究中国汉族人群中PAX4基因多态性及其与胰岛自身抗体阴性的酮症倾向糖尿病患者的关系。
我们采用变性高效液相色谱法（DHPLC）筛查了112例非糖尿病对照者（NC组）和141例酮症倾向糖尿病患者（KPD组）的PAX4基因外显子3和9的变异情况，这些患者谷氨酸脱羧酶抗体（GAD-Ab）和蛋白酪氨酸磷酸酶抗体（IA-2Ab）均为阴性。对异常峰的序列进行DNA测序分析。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法对308例非糖尿病对照者和141例KPD患者的PAX4基因A1168C单核苷酸多态性进行基因分型。
患者和对照者的PAX4基因外显子3均未发现变异。PAX4基因外显子9存在一个单核苷酸多态性位点A1168C，该位点导致错义突变P321H（rs712701）。KPD患者与对照者之间A1168C多态性的基因型和等位基因频率未观察到显著差异（P = 0.532，0.426）。当按性别对患者进行分层时，KPD组CC基因型和C等位基因频率存在差异（P = 0.009，0.028）。根据诊断时的年龄，KPD组中年龄<20岁和≥20岁的患者在CC基因型和C等位基因频率上存在差异（P = 0.034，0.032）。CC基因型组的FCP水平显著高于AA基因型组（P = 0.005）。
PAX4基因的A1168C多态性可能在中国汉族人群胰岛自身抗体阴性的KPD遗传易感性中不起重要作用。然而，A1168C变异可能导致男性或年龄<20岁的胰岛自身抗体阴性KPD患者易患该病。
