title: Mutations in the small heterodimer partner gene increase morbidity risk in Japanese type 2 diabetes patients.
abstract: 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.
authors.affiliation: Department of Diabetes and Endocrinology Division of Molecule and Structure Gifu University School of Medicine, Gifu.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Enya
authors.forename: Yukio
authors.initials: Y
authors.lastname: Horikawa
authors.forename: Eiji
authors.initials: E
authors.lastname: Kuroda
authors.forename: Kayoko
authors.initials: K
authors.lastname: Yonemaru
authors.forename: Naoko
authors.initials: N
authors.lastname: Tonooka
authors.forename: Hideaki
authors.initials: H
authors.lastname: Tomura
authors.forename: Naohisa
authors.initials: N
authors.lastname: Oda
authors.forename: Norihide
authors.initials: N
authors.lastname: Yokoi
authors.forename: Kazuya
authors.initials: K
authors.lastname: Yamagata
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Shihara
authors.forename: Katsumi
authors.initials: K
authors.lastname: Iizuka
authors.forename: Toshiji
authors.initials: T
authors.lastname: Saibara
authors.forename: Susumu
authors.initials: S
authors.lastname: Seino
authors.forename: Jun
authors.initials: J
authors.lastname: Takeda
mesh_terms: 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
chemical_list: D018160:Receptors, Cytoplasmic and Nuclear; C099713:nuclear receptor subfamily 0, group B, member 2