上海交通大学学报（医学版）

›› 2013, Vol. 33 ›› Issue (5): 631-.doi: 10.3969/j.issn.1674-8115.2013.05.024

• 论著（临床研究） • 上一篇    下一篇

早发2型糖尿病和糖尿病前期患者Pax6基因突变/变异的筛查与临床特点研究

陆玉凤1,2, 顾 静3, 陈 虹1, 庄兰艮1, 赵明明1, 张 荣1, 李 灿1, 李 鸣1, 郑泰山1, 蒋曦媛2, 刘丽梅1   

  1. 1.上海交通大学附属第六人民医院内分泌代谢科 |上海市糖尿病研究所, 上海 200233； 2.南京中医药大学附属昆山市中医医院内分泌科, 昆山 215300； 3.华东疗养院内科, 无锡 214065
  • 出版日期:2013-05-28 发布日期:2013-05-28
  • 通讯作者: 刘丽梅, 电子信箱: lmliu@sjtu.edu.cn。
  • 作者简介:陆玉凤(1987—), 女, 硕士； 电子信箱: luyufeng870101@163.com； 顾静（1977—）, 女, 学士； 电子信箱: g950324@163.com。
  • 基金资助:

    国家自然科学基金(81270876, 30771022, 30971384)；上海市科委优秀学科带头人基金(10XD1403400)

Screening and clinical characteristics of mutations/variations of Pax6 gene in patients with early-onset type 2 diabetes and pre-diabetes

LU Yu-feng1,2, GU Jing3, CHEN Hong1, ZHUANG Lan-gen1, ZHAO Ming-ming1, ZHANG Rong1, LI Can1, LI Ming1, ZHENG Tai-shan1, JIANG Xi-yuan2, LIU Li-mei1   

  1. 1.Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, the Sixth People´s Hospital, Shanghai Jiaotong University, Shanghai 200233, China； 2.Department of Endocrinology and Metabolism, Kunshan Hospital of Traditional Chinese Medicine, Nanjing University of Traditional Chinese Medicine, Kunshan 215300, China； 3.Department of Internal Medicine, Huadong Sanatorium, Wuxi 214000, China
  • Online:2013-05-28 Published:2013-05-28
  • Supported by:

    National Natural Science Foundation of China, 81270876, 30771022, 30971384；Program of Shanghai Subject Chief Scientist, 10XD1403400

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摘要：

目的 在早发、呈常染色体显性遗传的2型糖尿病及糖尿病前期人群中筛查成对盒6 （Pax6）基因外显子及外显子－内含子拼接区的突变/变异，研究其临床特点。方法 以早发2型糖尿病患者（n=96）、糖尿病前期患者（n=26）和非糖尿病对照者（对照组，n=100）为研究对象。应用PCR产物直接测序法对三组人群进行Pax6基因的突变/变异筛查，比较临床特点及突变/变异基因型频率。根据基因型进行再分组，分析临床表型特点。结果 在早发2型糖尿病组发现exon 6同义突变Arg67Arg （aga→agg；A→G，99.0% 和1.0%）；在糖尿病前期组发现exon 7的同义突变 Thr166Thr （act→acc；T→C，96.2% 和3.8%)；在非糖尿病对照组中未发现以上两种突变。早发2型糖尿病组空腹血糖（FPG）和餐后2 h血糖（2hPG）显著高于非糖尿病对照组（P<0.05）；而早发糖尿病前期组的2hPG、空腹胰岛素（FINS）和餐后2 h胰岛素（2hINS）显著高于非糖尿病对照组（P<0.05）。与Arg67Arg-AA基因型携带者相比，AG基因型者的2hINS显著降低（P<0.05）, 空腹C肽（FCP）和餐后2 h C肽（2hCP）及FINS呈下降趋势，FPG及2hPG呈升高趋势。与Thr166Thr-TT基因型携带者相比，TC基因型者2hCP和2hINS显著降低（P<0.05）。结论 Pax6基因的Arg67Arg与Thr166Thr突变可能影响胰岛素基因的转录，导致胰岛素分泌减少所致的糖代谢异常，与早发2型糖尿病以及糖尿病前期的发生和进展有关。

关键词: 成对盒基因6/Pax6基因, 突变, 常染色体显性遗传, 早发2型糖尿病, 糖尿病前期

Abstract:

Objective To screen the mutations or variations in paired box 6 (Pax6) gene, and investigate the clinical characteristics of patients with early-onset type 2 diabetes mellitus or pre-diabetes. Methods Patients with early-onset type 2 diabetes mellitus (n=96) and pre-diabetes (n=26) and non-diabetic controls (n=100) were selected. The mutations or variations in Pax6 gene were screened with PCR product direct sequencing, and the clinical characteristics and distributions of mutations or variations in the gene were compared. Subgroups were divided according to genotypes, and the characteristics of clinical phenotypes were analysed. Results Arg67Arg mutation in exon 6 (aga→agg; A→G, 99.0% and 1.0%) was detected in patients with early-onset type 2 diabetes mellitus, Thr166Thr mutation in exon 7 (act→acc; T→C, 96.2% and 3.8%) was detected in patients with pre-diabetes, while these two mutations were not detected in the non-diabetic controls. The fasting plasma glucose (FPG) and 2 h postprandial blood glucose (2hPG) in patients with early-onset type 2 diabetes mellitus were significantly higher than those in non-diabetic controls (P＜0.05), while 2hPG, fasting insulin (FINS) and 2 h postprandial insulin (2hINS) in patients with pre-diabetes were significantly higher than those in non-diabetic controls (P＜0.05). In comparison with Arg67Arg-AA carrier, AG carriers exhibited significantly decreased 2hINS(P<0.05), decreased tendencies in fasting C-peptide (FCP), 2 h postprandial C-peptide (2hCP) and FINS, and increased tendencies in FPG and 2hPG. Compared with Thr166Thr-TT carriers, 2hCP and 2hINS in TC carriers were significantly decreased (P<0.05). Conclusion Arg67Arg and Thr166Thr mutations in Pax6 gene may influence the transcription of insulin gene, decrease the insulin secretion, and result in the abnormal glucose metabolism, which may be associated with the development of early-onset type 2 diabetes and pre-diabetes.

Key words: paired box 6 (Pax6) gene, mutation, early-onset type 2 diabetes, pre-diabetes