b 3 -adrenergic-receptor polymorphism: a genetic marker for visceral fat obesity and the insulin resistance syndrome

Abstract

Obesity is a complex phenotype resulting from the combined effects of genes, behavioural and lifestyle factors, and their interactions [1]. The associations between obesity and increased risk of morbidity and mortality are well documented [2]; however, distribution of body fat is also of importance [3]. A syndrome with a clustering of multiple risk factors for coronary atherosclerosis has been described and defined by Reaven [4] as syndrome X; by Kaplan [5] as the deadly quartet; and by Matsuzawa et al. [6] as visceral fat obesity, which is more strongly associated with metabolic and cardiovascular diseases than subcutaneous fat obesity [7,8]. From clinical and basic experiments, the imbalance of sex hormones [9], aging [10], excessive intake of sucrose [11] and lack of physical exercise [10] have been suggested to be major factors for visceral fat accumulation. However, it is not known whether a major gene exists which promotes visceral fat accumulation, although Bouchard et al. [12] demonstrated six times more variation between twin pairs than within twin pairs for an Diabetologia (1997) Summary We investigated whether the polymorphism of the b 3 -adrenergic receptor (b 3 -AR) gene, which is associated with insulin resistance in non-diabetic subjects and an earlier onset of non-insulin-dependent diabetes mellitus in Pima Indians, was associated with visceral fat obesity and features of the insulin resistance syndrome in Japanese premenopausal obese women. There was no difference between 131 obese women and 256 control subjects , n = 48) women than in women homozygous for the Trp 64 Trp (121 ± 46 cm 2 , n = 77) genotype (p < 0.01). This was also reflected by increased total body fat but not by increased body mass index. The association between the Trp 64 allele and visceral fat mass by multiple regression analysis, was independent of age, body mass index and total fat mass (p < 0.004). Moreover, homozygous carriers of the Arg 64 allele had higher systolic blood pressure, higher fasting and post-load glucose and insulin concentrations, higher cholesterol, and triglyceride and lower HDL-cholesterol concentrations than homozygous carriers of the Trp 64 allele. Some of these differences were also observed between heterozygous Trp 64 Arg and homozygous Trp 64 Trp genotypes (glucose tolerance, insulin and cholesterol concentration). We conclude that in obese women the b 3 -AR polymorphism may be used as a genetic marker for visceral fat obesity and the insulin resistance syndrome. [Diabetologia (1997) 40: 200-204]

The frequency of Trp64Arg polymorphism of the β3-adrenergic receptor gene in healthy and obese Hungarian children and its association with cardiovascular risk factors

“…However, the lipid levels were similar in the two obese groups. Our results are in concert with the findings of Strazullo et al (2001) and Sakane et al (1997). We are aware of the weaknesses of the present study, which are as follows: (1) confounding factors, such as socioeconomical background, physical activity and nutrition, which could also play a role in the differences found in the present study, were not investigated; (2) other polymorphisms (eg uncoupling protein 1, 2 and 3 and peroxisome proliferator-activated receptor-gamma genes) that were not studied in the present sample may also interact.…”

The ADRB3 Trp64Arg variant and obesity in African-American breast cancer cases

“…11,[37][38][39] The high expression and activity of ADRB3 in visceral adipose tissue is consistent with our observed association between the ADRB3 variant and visceral, but not subcutaneous fat. Findings from a previous study of Japanese women 40 also indicated a significant association between the ADRB3 Trp64Arg substitution and visceral abdominal fat. In our African-American cases, the positive association between ADRB3 and obesity was found for the wild-type receptor, and in Japanese women, the association was found for the variant.…”

W64R Mutation in β-3-adrenergic receptor gene and weight in a large population sample

“…1 Other studies have found the R allele is not associated with BMI, fat distribution, metabolic variables, visceral fat cell size and lipolytic response to noradrenaline, in normal weight or obese non-diabetic individuals. 15 However, a number of Japanese studies have shown an association of the mutant allele with BMI, 13,16,17 with visceral fat, 18 and with a blunted response to treatment of obesity in women. 19 The high frequency of the W64R mutation reported in nonobese Japanese subjects, 17 together with uniform allele frequency with respect to BMI within ethnic groups suggests that the mutation itself is not a major determinant of obesity.…”