[Polymorphisms of adiponectin and resistin genes in patients with obesity and anorexia nervosa].
ABSTRACT Adiponectin and resistin are hormones that may represent a link between obesity and insulin resistance. Genes for these hormones are new candidate genes of insulin resistance and type 2 diabetes mellitus. The aim of our study was to determine the frequency of single nucleotide polymorphisms 45T > G and 276T > G of adiponectin gene and 62G > A and -180C > G of resistin gene in patients with obesity, anorexia nervosa and in lean women and to study the influence of particular genotypes on serum concentrations of these hormones.
Serum adiponectin, resistin, TNF-alfa and insulin levels were measured in 51 patients with obesity, 17 with anorexia nervosa and 17 lean women. DNA analysis was carried out by means of polymerase chain reaction (PCR) with restriction analysis of PCR product (RFLP). Adiponectin levels were lowest in obese women and highest in anorexia nervosa patients. Resistin concentrations were lowest in anorexia nervosa and highest in obese patients. Genotype analysis within respective groups showed no differences in assessed parameters when comparing different adiponectin and resistin polymorphisms. The only difference detected was significantly higher BMI in G/G genotype relative to T allele carries in 276 position of ADP gene in control group (23.48 +/- 0.85 vs. 19,7 +/- 0.95, p < 0.05). In anorexia nervosa patients, frequency of G allele in RETN -180 polymorphism was significantly higher relative to control group (p < 0.05).
Polymorphisms 45T > G a 276T > G of ADP gene and 62G>A and -180C > G RETN gene did not influence serum ADP and RETN concentrations. BMI was influenced by T allele presence in 276 position of ADP gene in control group only. Anorexia nervosa patients had higher frequency of G allele of RETN -180 polymorphism compared to healthy women.
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ABSTRACT: Anorexia nervosa (AN), bulimia nervosa (BN) and binge-eating disorder (BED) are characterized by abnormal eating behaviors often resulting in dramatic physical consequences for the patients. The etiology of eating disorders (EDs) is currently unknown; however, a strong genetic contribution is likely to be involved. To date, the majority of genetic studies have focused on candidate genes, and polymorphic variants of genes coding for substances likely to be involved in the etiopathogenesis of EDs have been assessed for association with AN, BN, BED and/or ED-related phenotypic traits. Results have been generally inconsistent and cannot be considered conclusive because of several methodological flaws and differences, such as small sample sizes, ethnic heterogeneity of studied populations, lack of statistical correction for multiple testing, adoption of different diagnostic criteria and population stratification. Although, at present, no convincing evidence for associations of candidate genes with EDs has been provided, the 5-HT(2A) receptor gene and the BDNF gene seem to be promising candidates for genetic influences on AN, since polymorphic variants of these genes have been found quite consistently, although not specifically, linked to AN restricting subtype in large sample studies. Moreover, pharmacogenetic investigations have suggested a possible role of some gene polymorphisms in predicting the response to treatment with selective serotonin reuptake inhibitors in BN, but results are still preliminary. The heterogeneity of ED phenotypes is believed to represent the most relevant variable responsible for contradictory and not conclusive results. Future studies should focus on more homogeneous subgroups, either relying on specific ED traits or identifying endophenotypes. This will be useful also for prevention and treatment of EDs.Pharmacogenomics 11/2008; 9(10):1487-520. · 3.43 Impact Factor
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ABSTRACT: The purpose of this study was to estimate the heritability of obesity-related phenotypes and investigate the association of adiponectin gene polymorphisms +45T>G and +276G>T with these measures in Chinese twins. 1260 twin pairs were recruited from two cities through the Chinese National Twin Registry System from 2001 to 2005. Two SNPs at the adiponectin locus (+45T>G and +276G>T) were genotyped. Structural equation modeling (SEM) was used to estimate heritability and the best-fitting variance component model. The regular association among all twins was analysed with generalised estimating equations (GEE). Sib-transmission/disequilibrium test (TDT) within dizygotic (DZ) twin pairs discordant for their genotype was performed using SEM. Additive genetic, common and unique environmental (ACE) model-based heritability of body mass index (BMI) was 61%, while additive genetic and unique environmental (AE)-model-based heritability of waist circumference (WC) and waist-hip ratio (WHR) were 75% and 61%, respectively. There was no association of adiponectin gene +45T>G and +276G>T genotypes with obesity-related phenotypes in all twins or discordant DZ twins. Our twins data did not support that there was an association between adiponectin gene polymorphisms +45T>G and +276G>T and the obesity-related phenotypes. Further studies are required to better understand the role of adiponectin gene polymorphisms in obesity.Annals of Human Genetics 03/2010; 74(2):146-54. · 1.93 Impact Factor
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ABSTRACT: Resistin causes insulin resistance and diabetes in mice whereas in humans it is linked to inflammation and atherosclerosis. Few human genetic studies of resistin in inflammation and atherosclerosis have been performed. We hypothesized that the -420C>G putative gain-of-function resistin variant would be associated with inflammatory markers and atherosclerosis but not with metabolic syndrome or adipokines in humans. We examined the association of three resistin polymorphisms, -852A>G, -420C>G and +157C>T, and related haplotypes with plasma resistin, cytokines, C-reactive protein (CRP), adipokines, plasma lipoproteins, metabolic syndrome and coronary artery calcification (CAC) in nondiabetic Caucasians (n = 851). Resistin levels were higher, dose-dependently, with the -420G allele (CC 5.9 +/- 2.7 ng/ml, GC 6.5 +/- 4.0 ng/ml and GG 7.2 +/- 4.8 ng/ml, trend P = 0.04) after age and gender adjustment [fold higher for GC + GG vs. CC; 1.07 (1.00-1.15), P < 0.05)]. The -852A>G single nucleotide polymorphism (SNP) was associated with higher soluble tumour necrosis factor-receptor 2 (sol-TNFR2) levels in fully adjusted models [1.06 (95% CI 1.01-1.11), P = 0.01)]. The estimated resistin haplotype (GGT) was associated with sol-TNFR2 (P = 0.04) and the AGT haplotype was related to CRP (P = 0.04) in the fully adjusted models. Resistin SNPs and haplotypes were not associated with body mass index (BMI), fasting glucose, insulin resistance, metabolic syndrome, adipokines or CAC scores. Despite modest associations with plasma resistin and inflammatory biomarkers, resistin 5' variants were not associated with metabolic parameters or coronary calcification. This suggests that resistin is an inflammatory cytokine in humans but has little influence on adiposity, metabolic syndrome or atherosclerosis.Clinical Endocrinology 08/2008; 70(5):698-705. · 3.35 Impact Factor