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

• Original article (Clinical research) • Previous Articles     Next Articles

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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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