Molecular and phenotypic characteristics of maturity-onset diabetes of the young compared with early onset type 2 diabetes in China.

Abstract

The aim of the present study was to investigate the contribution of maturity-onset diabetes of the young (MODY) genes to the etiology of 14 Chinese MODY families and to assess phenotypic differences between patients with MODY but without a known genetic cause of diabetes (MODYX) and those with early onset type 2 diabetes (T2D). The study included 14 MODY probands from unrelated families and 59 patients (age of onset ≤35 years) diagnosed as early onset T2D. A standard meal test and metabolic studies were performed to characterize the clinical features of all patients. All probands with MODY were analyzed for nucleotide variations in promoters, exons, and exon-intron boundaries of 13 known MODY genes by direct DNA sequencing. Mutations in 13 known MODY genes were not present in the 14 Chinese families and they were classified as MODYX. However, different polymorphisms were identified, with I27L (42.9%; 12/28) and S487N (46.4%; 13/28) of hepatocyte nuclear factor 4α (HNF1α/MODY3) being two most frequent polymorphisms. Two new polymorphisms, namely T412I and D504H, were detected in carboxyl ester lipase (CEL/MODY8). Compared with patients with early onset T2D, patients with MODYX were diagnosed with diabetes at a younger age (28.3 ± 6.5 vs 24.3 ± 6.5 years; P < 0.05) and had a lower body mass index (BMI; 28.3 ± 6.1 vs 24.1 ± 4.3 kg/m(2) ; P < 0.01) and homeostatic model assessment of β-cell function (47.6 [22.2-89.4] vs 18.5 [6.5-33.7]; P < 0.05). Herein we report on 14 Chinese families with MODYX and describe its phenotype. Compared with early onset T2D, MODYX is characterized by lower BMI and decreased insulin-secreting capacity.