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Mutations of maturity‐onset diabetes of the young (MODY) genes in Thais with early‐onset type 2 diabetes mellitus
Author(s) -
Plengvidhya Nattachet,
Boonyasrisawat Watip,
Chongjaroen Nalinee,
Jungtrakoon Prapaporn,
Sriussadaporn Sutin,
Vannaseang Sathit,
Banchuin Napatawn,
Yenchitsomanus Pathai
Publication year - 2009
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/j.1365-2265.2008.03397.x
Subject(s) - thais , maturity onset diabetes of the young , missense mutation , proband , genetics , biology , medicine , type 2 diabetes , diabetes mellitus , endocrinology , exon , mutation , gene , demography , sociology
Summary Objective Six known genes responsible for maturity‐onset diabetes of the young (MODY) were analysed to evaluate the prevalence of their mutations in Thai patients with MODY and early‐onset type 2 diabetes. Patients and methods Fifty‐one unrelated probands with early‐onset type 2 diabetes, 21 of them fitted into classic MODY criteria, were analysed for nucleotide variations in promoters, exons, and exon–intron boundaries of six known MODY genes, including HNF‐4α , GCK , HNF‐1α , IPF‐1 , HNF‐1β , and NeuroD1/β2 , by the polymerase chain reaction‐single strand conformation polymorphism (PCR‐SSCP) method followed by direct DNA sequencing. Missense mutations or mutations located in regulatory region, which were absent in 130 chromosomes of non‐diabetic controls, were classified as potentially pathogenic mutations. Results We found that mutations of the six known MODY genes account for a small proportion of classic MODY (19%) and early‐onset type 2 diabetes (10%) in Thais. Five of these mutations are novel including GCK R327H, HNF‐1α P475L, HNF‐1α G554fsX556, NeuroD1 –1972 G > A and NeuroD1 A322N. Mutations of IPF‐1 and HNF‐1β were not identified in the studied probands. Conclusions Mutations of the six known MODY genes may not be a major cause of MODY and early‐onset type 2 diabetes in Thais. Therefore, unidentified genes await discovery in a majority of Thai patients with MODY and early‐onset type 2 diabetes.