DNA polymorphism in the uncoupling protein 1 (UCP1) gene has no effect on obesity related phenotypes in the Swedish Obese Subjects cohorts

Abstract

OBJECTIVE: To investigate the relationships between the A±G point mutation at position 73826 bp in the 5 H¯a nking domain of the uncoupling protein 1 (UCP1 A-3826G) and some obesity phenotypes in the Swedish Obese Subjects (SOS) cohorts of obese and non-obese men and women. Previous studies have supported the hypothesis of an association between the UCP1 A-3826G polymorphism and body weight regulation in humans. DESIGN: Case-control study comparing obese subjects from the SOS registry and a sample of the Swedish general population (body mass index (BMI)`27 kgam 2 ) with respect to genotype and allele frequencies of the UCP1 A-3826G polymorphism. SUBJECTS: A total of 985 Swedish subjects including 674 obese (310 Male; 364 Female) and 311 non-obese subjects (54 Male; 257 Female) from the SOS cohorts. MEASUREMENTS: DNA was extracted from total blood and genotyped by PCR-RFLP. Obesity-related phenotypes include weight history for SOS obese cohort and current weight, BMI, waist circumference and waist to hip ratio (WHR) for obese and normal weight subjects. RESULTS: No signi®cant difference in the allelic frequencies between obese and non-obese subjects (0.25 vs 0.24; P 0.67). In both genders, current weight, BMI, waist circumference, WHR and weight gain over time (either measures of maximal weight ever achieved minus weight at 20 y or current weight minus weight at 20 y) were similar in carriers and non-carriers of the UCP1 A-3826G mutation (Pb0.05). Similar results were obtained when the three genotypes were compared. CONCLUSIONS: In contrast to what was found in other populations, the UCP1 A-3826G sequence variation is not associated with obesity-related phenotypes and weight gain over time in subjects from the SOS cohorts.

The uncoupling protein homologues: UCP1, UCP2, UCP3, StUCP and AtUCP

“…Several groups reported an additive effect of this UCP1 gene variant and the Trp-64 Tyr mutation of the β $ -adrenoceptor gene in obese individuals [185][186][187]. In contrast with what was found in other populations, no association of the UCP1 A3826G sequence variation with obesity was found in Swedish and German cohorts [188,189]. In other respects, several amino acid variants have been identified in human UCP1, but these genetic variations of the coding region are not common factors contributing to obesity in Caucasians [190,191].…”

Association of -3826 G Variant in uncoupling protein-1 with increased BMI in overweight Australian women

“…The ±3826 G variant of UCP-1 has been weakly associated with increased weight gain over time in morbidly obese women [4] and resistance to weight loss during moderate energy restriction [5] although it has not been independently associated with a reduced basal metabolic rate [6]. Furthermore, the ±3826 G variant has not been associated with BMI in the general population and the distribution of this variant is even between lean and obese subjects [4,7]. This suggests that the ±3826 G polymorphism of UCP-1 does not have a large role in obesity.…”

Putative role of polymorphisms in UCP1-3 genes for diabetic nephropathy

“…The UCP1 A ! G (À 3862) polymorphism in the promoter of the UCP1 gene has been associated with increased BMI (Hayakawa et al, 1999;Heilbronn et al, 2000) whereas other studies have failed to demonstrate any association between obesity and this UCP1 polymorphism (Gagnon et al, 1998;Urhammer et al, 1997). The I/D variant of UCP2 in the 3 0 untranslated region of exon 8 of UCP2 was found to be associated with increased sleeping metabolic rate and 24-h energy expenditure and with lower BMI in Pima Indians (Walder et al, 1998), and homozygous carriers of the insertion had increased BMI in a South Indian population (Cassell et al, 1999).…”