Genomic structure and mutations in adipose-specific gene, adiponectin

Abstract

BACKGROUND: Adiponectin is a collagen-like plasma protein speci®cally synthesized in adipose tissue. Plasma adiponectin concentrations are decreased in obesity whereas it is adipose-speci®c. OBJECTIVE: To clarify the signi®cance of the genetic variations in adiponectin gene on its plasma concentrations and obesity. SUBJECTS: Two hundred and nineteen unrelated adult Japanese subjects (123 men and 96 women, age: 20 ± 83 y, BMI: 16 ± 43 kgam 2 ) including 77 obese subjects (BMI b 26.4 kgam 2 ). MEASUREMENT: Human adiponectin gene was isolated from PAC DNA pools. Mutations in the adiponectin gene were screened by direct sequencing or restriction-fragment polymorphism. The levels of plasma adiponectin were determined by the enzyme-linked immunosorbent assay (ELISA). RESULTS: Adiponectin gene spanned 17 kb on chromosome 3q27, consisting of three exons and two introns. Within 2.1 kb of the 5 H -¯anking region, there were two octamer elements present in the promoter of adipsin. Two nucleotide changes were identi®ed. One was a polymorphism (GaT) occurring in exon 2, and the other was a missense mutation (R112C) in exon 3. The mean plasma adiponectin levels of the subjects carrying G allele were low (GaG: 4.5 mgaml; GaT: 5.9 mgaml; and TaT: 6.3 mgaml), but were not statistically signi®cant. The allelic frequency between the obese and the non-obese showed no signi®cant difference. The subject carrying R112C mutation showed markedly low concentration of plasma adiponectin. CONCLUSION: Two nucleotide changes have been identi®ed in the adiponectin gene. GaT polymorphism in exon 2 was associated with neither plasma adiponectin concentrations nor the presence of obesity. A subject carrying missense mutation (R112C) showed markedly low plasma adiponectin concentration.

Adiponectin Level and Gene Variability Are Obesity and Metabolic Syndrome Markers in a Young Population

“…Similar results were obtained in other studies in other ethnic groups with regard to associations of rare -11377G (9,18,36, 47,50), or -11391G>A (51) allele/genotype/haplotype carriers with obesity and obesityrelated phenotypes. In contrast, some other studies demonstrated that the common -11377C allele was strongly associated with obesity and MetS parameters (17,52). Our findings are also consistent with previous reports in different populations and different age groups (53,54,55) stating that ADIPOQ gene may play an important role in MetS.…”

Genome-wide association study for adiponectin levels in Filipino women identifies CDH13 and a novel uncommon haplotype at KNG1–ADIPOQ

“…Nonsynonymous amino acid substitutions may contribute to the variation of circulating adiponectin by affecting the spatial organization of the protein and interfering with posttranscriptional modification, multimerization or interaction of the protein with its receptors (16). Variants including G84R, G90S, H111Y and R112C have been reported to be associated with adiponectin level and suggested to be functionally relevant (16,33,34). However, these variants were rare in initial studies (MAF,0.02) and are not included as HapMap or 1000 Genomes Project Pilot imputed SNPs.…”

Genetic variations in the gene encoding TFAP2B are associated with type 2 diabetes mellitus

“…Differentiated adipocytes can function in an endocrine manner to secrete several cytokines, called ''adipokines,'' which include TNF-a, IL-6, leptin, adiponectin, and others (Spiegelman and Flier 1996;Matsuzawa et al 1999). These genes are found to contain binding sites for TFAP2 in their promoter (Kroeger and Abraham 1996;Isse et al 1995;Takahashi et al 2000). Given such observations, we suggest that TFAP2B plays a key role in the pathogenesis of type 2 A d ip o c y t e B r a in H e a r t K id n e y L iv e r L u n g P a n c r e a s P la c e n t a S k e le t a l m u s c le T h y m u s F e t a l B r a in F e t a l k id n e y F e t a l lu n g A d ip o c y t e B r a in H e a r t K id n e y L iv e r L u n g P la c e n t a S k e le t a l m u s c le ND P a n c r e a s Fig.…”