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Mutations in the small heterodimer partner gene increase morbidity risk in Japanese type 2 diabetes patients
Author(s) -
Enya Mayumi,
Horikawa Yukio,
Kuroda Eiji,
Yonemaru Kayoko,
Tonooka Naoko,
Tomura Hideaki,
Oda Naohisa,
Yokoi Norihide,
Yamagata Kazuya,
Shihara Nobuyuki,
Iizuka Katsumi,
Saibara Toshiji,
Seino Susumu,
Takeda Jun
Publication year - 2008
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.20865
Subject(s) - biology , type 2 diabetes , genetics , gene , diabetes mellitus , mutation , bioinformatics , medicine , endocrinology
Mutations in the small heterodimer partner gene (NR0B2; alias SHP) are associated with high birth weight and mild obesity in Japanese children. SHP mutations may also be associated with later obesity and insulin resistance syndrome that induces diabetes. To investigate this possibility, the prevalence of SHP mutations in Japanese with and without type 2 diabetes mellitus and the functional properties of the mutant proteins were evaluated. Direct sequencing of two exons and flanking sequences of SHP in 805 diabetic patients and 752 non‐diabetic controls identified 15 different mutations in 44 subjects, including 6 novel mutations. Functional analyses of the mutant proteins revealed significantly reduced activity of nine of the mutations. Mutations with reduced activity were found in 19 patients (2.4%) in the diabetic group and in 6 subjects (0.8%) in the control group. The frequency difference between DM and control subjects adjusted for sex and age was statistically significant ( P =0.029, odds ratio 2.67, 95% CI 1.05–6.81, 1−β=0.91). We conclude that SHP mutations associated with mild obesity in childhood increase susceptibility to type 2 diabetes in later life in Japanese. © 2008 Wiley‐Liss, Inc.