| OBJECTIVES To screen mutations/variants of pax6 gene and study their clinical characteristics in early-onset type 2 diabetic patients and IFP/IGT patients in Chinese.METHODS PCR-direct sequencing was used to detect the pax6 gene mutations/variants in 96 unrelated early onset type 2 diabetic patients,16 unrelated IFG/IGT patients and 100 unrelated non-diabetic control subjects. Clinical characteristics and distributions of pax6 gene mutations/variants were compared among the diabetic patients, 16 IFG/IGT patients and non-diabetic control subjects . Clinical characteristics between mutant carriers and wild genotype carriers were compared as well.RESULTS 1.R67R silent mutation in exon 6 and T166T silent mutation in exon 7 of the pax6 gene were found in two early-onset type 2 diabetic patients and two IFG/IGT patients respectively, but they were not detected in non-diabetic control subjects. 2. The early-onset type 2 diabetic patients showed significantly eleveted fasting plasma-glucose (FPG) and 2 hours plasma glucose level(2h PG) (p<0.05). IGT/IFG patients showed significantly increased 2h PG , fasting insulin (FINS) and 2 hours insulin level(2hINS). 3. In the early-onset type 2 diabetic patients, the R67R-AG genotype carriers showed apparently reduced 2hINS level (p<0.05), while lower fasting C-peptide level(FCP) , 2 hours C-peptide(2hCP) level and FINS level (p>0.05 for each) when compared with AA genotype carriers. In addition, the R67R-AG genotype carriers showed higher FPG and 2h PG level than AA carriers (p>0.05). 4.In IFG/IGT patients, the T166T-TC genotype carriers showed significantly reduced 2hINS and 2hCP level(p<0.05 for each), while lower FCP and FINS level (p>0.05 for each) when compared with TT carriers.CONCLUSIONS R67R or T166T mutation in Pax6 gene may affect the transcription and expression of insulin gene and resulted in reduction in insulin secretion, which may contribute to the development of early-onset type 2 diabetes or IGT/IFG patients respectively. |
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