上海地区早发2型糖尿病Isl-1基因突变筛查及患者临床特征

目的 筛查上海地区早发2型糖尿病Isl-1基因突变的发生情况并分析患者的临床特点.方法 选择上海地区96例早发2型糖尿病患者作为研究对象,以100名健康志愿者作为正常对照.收集受试者年龄、性别、血压等一般资料以及糖、脂代谢等实验室检查资料,并进行组间比较.应用PCR直接测序法,对两组受试者Isl-1基因突变情况进行筛查,观察突变基因位点、基因型分布频率、等位基因频率以及携带突变基因者的临床特点.结果 与正常对照组比较,早发2型糖尿病组患者年龄较轻,空腹血糖、空腹胰岛素及三酰甘油水平均明显升高（P＜0.05或P＜0.01）;空腹血浆C肽水平虽高于正常对照组,但差异无统计学意义（P＞0.05）.PCR直接测序筛查结果显示,正常对照组未见Isl-1基因突变;早发2型糖尿病组筛查发现2例患者携带Isl-1外显子5的E283D错义突变基因（A→T）,其中T等位基因频率为1.0%,AT基因型分布频率为2.1%;两突变基因携带者空腹血浆C肽分别为0.6 ng/mL和0.2 ng/mL,均低于其0.82 ng/mL的正常值下限（P＜0.05）.结论 上海地区早发2型糖尿病患者中筛查出Isl-1基因外显子5的E283D突变,且突变基因携带者的空腹血浆C肽水平均低于正常值下限.

Screening and clinical characteristics of Isl-1 gene mutations in early-onset type 2 diabetes mellitus in Shanghai

Objective To investigate the prevalence and clinical characteristics of Isl-1 gene mutations in early-onset type 2 diabetes mellitus in Shanghai. Methods Ninety-six patients with early-onset type 2 diabetes mellitus were enrolled. General data such as age, gender and blood pressure and laboratory data such as glucose and lipid metabolism were collected, and comparisons were made between groups. PCR-direct sequencing was employed to detect the Isl-1 gene mutations in two groups, loci of gene mutations, frequencies of genotype and allele were observed, and the clinical characteristics of mutation gene carriers were investigated. Another 100 healthy volunteers were served as normal controls. Results Compared with normal controls, patients with early-onset type 2 diabetes mellitus were younger, with significantly higher levels of fasting blood glucose, fasting insulin and triglyceride (P<0.05 or P<0.01). Though fasting C-peptide level in patients with early-onset type 2 diabetes mellitus was higher than that in normal controls, there was no significant difference between them (P>0.05). PCR-direct sequencing revealed that there were no Isl-1 gene mutations in normal controls, while E283D missense mutation (A→T) in exon 5 of Isl-1 gene was found in two patients with early-onset type 2 diabetes mellitus, with 1.0% for frequency of T allele and 2.1% for frequency of AT genotype. Fasting C-peptide levels of two mutation gene carriers were 0.6 ng/mL and 0.2 ng/mL, respectively, and were significantly lower than the lower normal limit (0.82 ng/mL) (P<0.05). Conclusion E283D mutation in exon 5 of Isl-1 gene can be screened from patients with early-onset type 2 diabetes mellitus in Shanghai, and fasting C-peptide levels of mutation gene carriers are lower than the lower normal limit.