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。
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 plasnm 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 earriers exhibited significantly decreased 2bINS（ 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 deereased （P 〈 O. 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 glueose metabolism, which may be associated with the development of early-onset type 2 diabetes and pre-diabetes.
出处
《上海交通大学学报（医学版）》
CAS
CSCD
北大核心
2013年第5期631-635,共5页
Journal of Shanghai Jiao tong University:Medical Science
基金
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)~~
