Mutations in the small heterodimer partner gene increase morbidity risk in Japanese type 2 diabetes patients.
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-beta=0.91). We conclude that SHP mutations associated with mild obesity in childhood increase susceptibility to type 2 diabetes in later life in Japanese.
Enya
Mayumi
M
Department of Diabetes and Endocrinology Division of Molecule and Structure Gifu University School of Medicine, Gifu.
Horikawa
Yukio
Y
Kuroda
Eiji
E
Yonemaru
Kayoko
K
Tonooka
Naoko
N
Tomura
Hideaki
H
Oda
Naohisa
N
Yokoi
Norihide
N
Yamagata
Kazuya
K
Shihara
Nobuyuki
N
Iizuka
Katsumi
K
Saibara
Toshiji
T
Seino
Susumu
S
Takeda
Jun
J
D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D004252:DNA Mutational Analysis; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009765:Obesity / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D012307:Risk Factors
D018160:Receptors, Cytoplasmic and Nuclear; C099713:nuclear receptor subfamily 0, group B, member 2