Allele-specific differential expression of a common adiponectin gene polymorphism related to obesity

Abstract

Adiponectin gene polymorphisms have recently been reported to be associated with obesity, insulin sensitivity, and the risk of type 2 diabetes. We examined a T94G polymorphism of the adiponectin gene in 245 ostensibly normal nondiabetic subjects. The G allele frequency was lower among subjects with higher BMI (> or =27) than in those with lower BMI. BMI was inversely correlated with the dose of G allele. Multivariate linear regression analyses showed that the adiponectin genotypes were significantly related to BMI after adjusting for age and gender. The dose of the G allele was associated with a reduction of approximately 1.12 kg/m(2) in BMI. We further found that the relative mRNA levels of G allele were consistently higher than those of T allele in the omental adipose tissue from 21 heterozygous subjects. Finally, we observed that the expression levels of adiponectin affected insulin-stimulated glucose uptake in differentiated 3T3-L1 adipocytes. In conclusion, the allele-specific differential expression of this common polymorphism could be responsible for its biological effects observed in this and the other studies.

A polymorphism in the adiponectin gene influences adiponectin expression levels in visceral fat in obese subjects

“…Interestingly, despite a higher percent body fat, carriers of the APM1 G276T T allele had higher levels of 37 Although this is an appealing hypothesis we feel that it is too soon to make this conclusion, not least in view of the limited number of participants in this study, which was not designed to answer this question primarily. In light of our present data and previously published data on the T45G polymorphism, 17,24 we were also interested in combinatorial effects between these polymorphisms and adiponectin expression. However, the frequency of the T45G allele was too low (0.08 for the G allele) in this material to perform such analyses.…”

“…Males [4] 139.578.2 Females [26] 115.2711.1 Fat % [31] 60.079.1 HOMA index [23] 4.074.2 Fasting glucose (mmol/l) [32] 4.970.6 Fasting insulin (mU/l) [24] 19.5716.8 Leptin (mg/l)…”

“…Several studies have reported an effect on serum adiponectin levels for different single nucleotide polymorphisms (SNPs) in the APM1 gene, 10,12,[17][18][19]23 but to our knowledge only one study has focused on the effect of a genetic marker on the APM1 mRNA expression in omental adipose tissue, reporting increased mRNA levels for the APM1 T94G G-allele. 24 Visceral adipose tissue is more metabolically active than subcutanoeus adipose tissue and is of greater importance for the development of obesity-related complications. 25 Therefore it is important to investigate both these adipose depots to detect differences in expression patterns and effects of genetic variants.…”

Polymorphisms of the gene encoding adiponectin and glycaemic outcome of Chinese subjects with impaired glucose tolerance: a 5-year follow-up study

“…T45G is a silent polymorphism with no amino acid change. However, it has been shown to influence the allelespecific differential expression of the adiponectin gene in human omental adipose tissue [20]. Previous studies have reported increased [8], decreased [21] or unchanged [18] levels of adiponectin in subjects with the T45G variant.…”

Promoter adiponectin polymorphisms and waist/hip ratio variation in a prospective French adults study

“…[7][8][9][10] Polymorphisms in exon 2 of the ADIPOQ gene, 45G4T and 276T4G, have been associated with obesity and insulin resistance. 11,12 Single nucleotide polymorphisms (SNPs) in the 5 0 region of the ADIPOQ gene, À11391G4A and À11377C4G, define haplotypes associated with diminished adiponectin concentrations and increased risk of type 2 diabetes in French Caucasians. 9 Since this risk of type 2 diabetes increases according to the level of corpulence, 9 the authors emphasized that adiponectin may represent a crucial link between the degree of obesity and the level of insulin resistance.…”