TY - JOUR

T1 - Mutational analysis of the coding region of the uncoupling protein 2 gene in obese NIDDM patients

T2 - impact of a common amino acid polymorphism on juvenile and maturity onset forms of obesity and insulin resistance

AU - Urhammer, S A

AU - Dalgaard, L T

AU - Sørensen, T I

AU - Møller, A M

AU - Andersen, T

AU - Tybjaerg-Hansen, A

AU - Hansen, T

AU - Clausen, J O

AU - Vestergaard, H

AU - Pedersen, O

PY - 1997/10

Y1 - 1997/10

N2 - Recently, a gene encoding a novel human uncoupling protein, designated UCP2, was discovered. The murine UCP2 was mapped to a region on mouse chromosome 7 which in several models has been shown to be linked to obesity and hyperinsulinaemia. Single strand conformation polymorphism (SSCP) analysis and direct sequencing of the coding region of the UCP2 gene in 35 obese Caucasian NIDDM patients of Danish ancestry revealed one nucleotide substitution, replacing an alanine with a valine at codon 55. The amino acid polymorphism was present in 24 of the 35 (69%) examined subjects. The allelic frequency of the A/V55 variant was 48.3% (95% CI: 42.5-54.1%) among 144 subjects with juvenile onset obesity, 45.6% (40.5-50.7%) among 182 subjects randomly selected at the draft board examination, and 45.5% (37.1-53.9%) among lean control subjects selected from the same study cohort. Within these cohorts there were no differences in BMI values at different ages among wild-type carriers and A/V55 carriers. In a population-based sample of 369 young healthy Caucasians the variant showed no association with alterations in BMI, waist-to-hip ratio, fat mass or weight gain during childhood or adolescence. The A/V55 polymorphism was not related to alterations in fasting values of serum insulin and C-peptide or to an impaired insulin sensitivity index. We conclude that genetic variability in the human UCP2 gene is not a common factor contributing to NIDDM in obese Danish Caucasian subjects and the common A/V55 amino acid polymorphism of the gene is not implicated in the pathogenesis of juvenile or maturity onset obesity or insulin resistance in Caucasians.

AB - Recently, a gene encoding a novel human uncoupling protein, designated UCP2, was discovered. The murine UCP2 was mapped to a region on mouse chromosome 7 which in several models has been shown to be linked to obesity and hyperinsulinaemia. Single strand conformation polymorphism (SSCP) analysis and direct sequencing of the coding region of the UCP2 gene in 35 obese Caucasian NIDDM patients of Danish ancestry revealed one nucleotide substitution, replacing an alanine with a valine at codon 55. The amino acid polymorphism was present in 24 of the 35 (69%) examined subjects. The allelic frequency of the A/V55 variant was 48.3% (95% CI: 42.5-54.1%) among 144 subjects with juvenile onset obesity, 45.6% (40.5-50.7%) among 182 subjects randomly selected at the draft board examination, and 45.5% (37.1-53.9%) among lean control subjects selected from the same study cohort. Within these cohorts there were no differences in BMI values at different ages among wild-type carriers and A/V55 carriers. In a population-based sample of 369 young healthy Caucasians the variant showed no association with alterations in BMI, waist-to-hip ratio, fat mass or weight gain during childhood or adolescence. The A/V55 polymorphism was not related to alterations in fasting values of serum insulin and C-peptide or to an impaired insulin sensitivity index. We conclude that genetic variability in the human UCP2 gene is not a common factor contributing to NIDDM in obese Danish Caucasian subjects and the common A/V55 amino acid polymorphism of the gene is not implicated in the pathogenesis of juvenile or maturity onset obesity or insulin resistance in Caucasians.

KW - Adult

KW - Age of Onset

KW - Blood Glucose

KW - C-Peptide

KW - Diabetes Mellitus, Type 2

KW - European Continental Ancestry Group

KW - Female

KW - Genotype

KW - Humans

KW - Insulin

KW - Insulin Resistance

KW - Ion Channels

KW - Male

KW - Membrane Transport Proteins

KW - Middle Aged

KW - Mitochondrial Proteins

KW - Mutation

KW - Obesity

KW - Polymorphism, Genetic

KW - Polymorphism, Single-Stranded Conformational

KW - Proteins

U2 - 10.1007/s001250050811

DO - 10.1007/s001250050811

M3 - Journal article

C2 - 9349606

VL - 40

SP - 1227

EP - 1230

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

IS - 10

ER -