Influence of the interaction between the adiponectin G276T polymorphism and body mass index on lipid levels in healthy children

Adiponectin is an adipose tissue-specific hormone which is inversely associated with metabolic alterations related to atherosclerosis. Polymorphisms in the adiponectin gene (AdipoQ) have been related to low adiponectin levels as well as several cardiovascular risk factors, but this association remains controversial. In our study we investigated the relationship between the AdipoQ T45G (rs: 2241766) and G276T (rs: 1501299) polymorphisms and adiponectin concentrations, blood pressure, and lipid and insulin levels, in a population-based sample of 12- to 16-year-old children. The study included 815 healthy Spanish children (388 boys and 427 girls). Plasma glucose and lipid levels were determined by standard methods. Insulin concentrations were measured by RIA, and serum adiponectin levels were determined by ELISA. The AdipoQ T45G and AdipoQ G276T polymorphisms were determined by TaqMan^® allelic discrimination assays. ANOVA or t test allowed for comparison of the studied parameters across genotypes or genotype groups, respectively. A linear regression analysis was performed to examine the independent relationships of the lipid variables with BMI (body mass index), AdipoQ G276T polymorphism and the interaction between the two. When independently comparing the effect of these polymorphisms in normal-weight and overweight children, we observed that overweight boys carriers of the minor allele T had significantly lower TC, LDL-C and apo A-I levels than non-carriers, but these differences were not apparent in normal-weight boys. Furthermore, linear regression analysis demonstrated that interaction between the BMI and the AdipoQ G276T polymorphism is a significant factor explaining the variations of TC and LDL-C levels. To our knowledge, this is the first study to report an association between the AdipoQ G276T polymorphism and lipid levels in overweight boys alone, thereby suggesting that the influence of the AdipoQ polymorphisms on cardiovascular risk factors may be dependent on BMI.     

Adiponectin and resistin gene polymorphisms in patients with anorexia nervosa and obesity and its influence on metabolic phenotype

Genes for adiponectin and resistin are candidate genes of insulin resistance and type 2 diabetes mellitus. The aim of our study was to determine the frequency of single nucleotide polymorphisms (SNP) 45T>G and 276G>T of the adiponectin gene and 62G>A and -180C>G of the resistin gene in patients with obesity (OB), anorexia nervosa (AN) and in control healthy normal-weight women (NW) and to study the influence of particular genotypes on serum concentrations of these hormones and on insulin sensitivity. Serum adiponectin, resistin, tumor necrosis factor alpha (TNF-alpha), insulin, cholesterol, glycated hemoglobin (HbA1c) and blood glucose levels were measured in 77 patients with OB, 28 with AN and 38 NW. DNA analysis was carried out by polymerase chain reaction with restriction analysis of PCR product. The presence of SNP ADP+276 G>T allele was accompanied by higher cholesterol levels in AN patients, higher adiponectin concentrations in OB patients and lower HbA1c levels in NW. SNP of the resistin gene 62G>A was associated with lower HbA1c in NW and higher cholesterol concentrations in OB group. The carriers of the minor G allele in the position -180 of the resistin gene within AN group had significantly higher BMI relative to non-carriers. We conclude that polymorphisms in adiponectin and resistin genes can contribute to metabolic phenotype of patients with obesity and anorexia nervosa.     

Lack of association of glutamate decarboxylase 2 gene polymorphisms with severe obesity in utah

Three polymorphisms of the glutamate decarboxylase 2 gene, which encodes the glutamic acid decarboxylase enzyme, have been associated with severe obesity in a large French cohort. One of these polymorphisms was shown to have functional consequences on promoter expression. Another polymorphism was associated with insulin levels and secretion. These associations were examined in 855 severely obese Utah subjects (mean BMI = 48 kg/m(2)) and a normal-weight and normoglycemic subset (N = 130, mean BMI = 22 kg/m(2)) of a random sample of the Utah population (N = 462). Comparisons of the normal-weight random group with the severely obese group did not result in significant genotype or allele frequency differences for any of the three polymorphisms, C61450A, T83897A, or A-243G (all p > or = 0.18). Haplotypes were also not related to severe obesity (p = 0.10). None of the polymorphisms was significantly related to fasting glucose, insulin levels, or homeostasis model assessment insulin resistance or secretion indices. This study of normal-weight and severely obese subjects from Utah does not provide evidence for involvement of the three genotyped polymorphisms in the glutamate decarboxylase 2 gene with obesity or with insulin- and glucose-related measures associated with obesity.     

ABCA1 C69T gene polymorphism and risk of type 2 diabetes mellitus in a Saudi population

Type 2 diabetes mellitus (T2DM) is a disease induced by complex interactions between environmental factors and certain genetic factors. Genetic variants in the Adenosine Binding Cassette Transporter Proteins 1 (ABCA1) have been associated with abnormalities of serum lipid levels of high-density lipoprotein (HDL-C). Decreased serum levels of HDL-C have often been observed in T2DM cases, and this condition has been considered to be involved in the mechanism of insulin resistance (IR). Therefore, we investigated possible association between ABCA1 C69T gene polymorphism and T2DM in a Saudi population. This study was carried out with 380 healthy control subjects and 376 T2DM patients. Genotyping of ABCA1 C69T polymorphism was carried out by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism technique. We observed that the frequency of the T allele of the ABCA1 C69T gene was significantly higher in healthy subjects compared to T2DM patients (0.28 vs 0.45; p<0.0001; OR (95% CI) = 0.4624 (0.3732–0.5729), and therefore the T allele may be a protective factor against T2DM in the Saudi population.     

Association of INSIG2 Polymorphism with Overweight and LDL in Children

Background

Dyslipidemia and overweight are common issues in children. Identifying genetic markers of risk could lead to targeted interventions. A polymorphism of SNP rs7566605 near insulin-induced gene 2 (INSIG2) has been identified as a strong candidate gene for obesity, through its feedback control of lipid synthesis.

Objective

To identify polymorphisms in INSIG2 which are associated with overweight (BMI ≥ 85% for age) and dyslipidemia in children. Hypothesis: The C allele of rs7566605 would be significantly associated with BMI and LDL.

Design/Methods

We genotyped 15 SNPs in/near INSIG2 in 1,058 healthy children (53% non-Hispanic white (NHW), 37% overweight) participating in a school based study. Genotype was compared with BMI and lipid markers, adjusting for age, gender, and puberty.

Results

We found a significant association between the SNP rs12464355 and LDL in NHW children, p < 0.001. The G allele is protective (lower LDL). A different SNP was associated with overweight in NHW: rs17047757. SNP rs7566605 was not associated with overweight or lipid levels.

Conclusions

We identified novel genetic associations between INSIG2 and both overweight and LDL in NHW children. Polymorphisms in INSIG2 may be important in the development of obesity through its effects on lipid regulation.     

Haplotypes in the promoter region of the ADIPOQ gene are associated with increased diabetes risk in a German Caucasian population.

Adiponectin, which is encoded by the ADIPOQ gene, has been shown to modulate insulin sensitivity and glucose homeostasis. Plasma adiponectin levels are decreased in type 2 diabetes and obesity. Genetic variations within the ADIPOQ gene are associated with decreased adiponectin hormone levels. To analyze specific single-nucleotide polymorphisms (SNPs) and their association with T2D, 365 German subjects with T2D and 323 control subjects were screened. Three common SNPs - +45T>G in exon 2, and 2 promoter variants SNPs -11391G>A and -11377C>G - were analyzed. We found that the variant allele of SNP -11391G>A was significantly more frequent in the diabetic patient group than in the control group (p=0.003). Carrying the haplotype of SNP -11391A and SNP -11377C was associated with a 1.50-fold (p=0.03) increase in diabetes risk. The combination of the A-C haplotype and the G-C haplotype was associated with significantly elevated diabetes risk (OR=2.82 (95% CI: 1.35-5.91), p=0.006) after correction for BMI and age. Our observations suggest that diploid combinations of haplotype in the adiponectin gene promoter region contribute to the genetic risk of T2D in individuals from a German Caucasian population.     

The promoter region of the adiponectin gene is a determinant in modulating insulin sensitivity in childhood obesity

We investigated the association of the -11,391G>A, -11,377G>C, +45T>G, and +276G>T adiponectin single-nucleotide polymorphisms (SNPs) and expected haplotypes with the insulin resistance (IR) state in overweight/obese children; by using the haplotype background analysis, we also assessed the effect of each SNP independently. GG genotype at the -11,391 locus was associated with higher fasting insulin levels and homeostasis model assessment-IR index and lower adiponectin levels compared with GA + AA genotypes (p = 0.01, 0.002, and 0.03, respectively). Those heterozygous and homozygous for G allele at the -11,377 locus showed higher fasting glucose (p = 0.001 for both), fasting insulin (p = 0.001 for both), homeostasis model assessment-IR index (p < 0.001 for both), and triglyceride levels (p = 0.02 and 0.03, respectively) and lower adiponectin levels (p = 0.002 and 0.02, respectively) compared with C homozygotes. The +45G carriers showed higher fasting and 2-hour glucose levels (p = 0.01 for both) and lower adiponectin levels (p = 0.02) compared with non-carriers. Haplotype analysis suggested that, considering the same haplotypic background, each of the three polymorphisms exerted an independent effect on investigated parameters. The -11,391G>A, -11,377C>G, and +45T>G SNPs are associated with IR syndrome in overweight/obese children; they independently influence the investigated variables. The effect of +45T>G SNP seems to be marginal compared with the promoter SNPs. The GGT haplotype is associated with the highest degree of IR.     

The effects of ABCG5/G8 polymorphisms on plasma HDL cholesterol concentrations depend on smoking habit in the Boston Puerto Rican Health Study

Low HDL-cholesterol (HDL-C) is associated with an increased risk for atherosclerosis, and concentrations are modulated by genetic factors and environmental factors such as smoking. Our objective was to assess whether the association of common single-nucleotide polymorphisms (SNPs) at ABCG5/G8 (i18429G>A, i7892T>C, Gln604GluC>G, 5U145A>C, Tyr54CysA>G, Asp19HisG>C, i14222A>G, and Thr400LysC>A) genes with HDL-C differs according to smoking habit. ABCG5/G8 SNPs were genotyped in 845 participants (243 men and 602 women). ABCG5/G8 (i7892T>C, 5U145A>C, Tyr54CysA>G, Thr400LysC>A) SNPs were significantly associated with HDL-C concentrations (P < 0.001–0.013) by which carriers of the minor alleles at the aforementioned polymorphisms and homozygotes for the Thr400 allele displayed lower HDL-C. A significant gene-smoking interaction was found, in which carriers of the minor alleles at ABCG5/G8 (Gln604GluC>G, Asp19HisG>C, i14222A>G) SNPs displayed lower concentrations of HDL-C only if they were smokers (P = 0.001–0.025). Also, for ABCG8_Thr400LysC>A SNP, smokers, but not nonsmokers, homozygous for the Thr400 allele displayed lower HDL-C (P = 0.004). Further analyses supported a significant haplotype global effect on lowering HDL-C (P = 0.002) among smokers. In conclusion, ABCG5/G8 genetic variants modulate HDL-C concentrations, leading to an HDL-C-lowering effect and thereby a potential increased risk for atherosclerosis only in smokers.     

Association of LIPA Gene Polymorphisms With Obesity-Related Metabolic Complications Among Severely Obese Patients

The lipase A, lysosomal acid, cholesterol esterase enzyme (LIPA) is involved in the hydrolysis of triglycerides (TGs) and cholesteryl esters (CEs) delivered to lysosomes. LIPA deficiency in human causes two distinct phenotypes characterized by intracellular storage of CE and derangements in the control of cholesterol production, namely the Wolman disease (WD) and the CE storage disease (CESD). To test the potential association of LIPA gene polymorphisms with obesity-related metabolic complications, promoter, exons, and intronic flanking regions of the LIPA gene were first sequenced in 25 individuals. From the 14 common polymorphisms identified, 12 tagging single-nucleotide polymorphisms (tSNPs) were genotyped in a cohort of 1,751 obese individuals. After adjustments for the effect of age, sex, diabetes, and medication, the C allele of SNP rs1051338 was associated with lower blood pressure (BP; systolic (SBP) P = 0.004; diastolic (DBP) P = 0.006). Three of the tested SNPs were associated with modifications of the plasma lipid profile. The G/G genotype of rs2071509 was associated with higher high-density lipoprotein cholesterol (HDL-C) levels (P = 0.009) and minor allele of rs1131706 was also associated with higher HDL-C (P = 0.004) and an association between rs3802656 and total cholesterol (total-C)/HDL-C ratio was identified (P = 0.04). These results thus suggest that LIPA polymorphisms contribute to the interindividual variability observed in obesity-related metabolic complications.     

<Emphasis Type="Italic">ABCA1</Emphasis> gene polymorphisms and their associations with coronary artery disease and plasma lipids in males from three ethnic populations in Singapore

Mutations in the ATP-binding cassette transporter ABCA1 underlie Tangier disease and familial hypoalphaliproteinemia (FHA), disorders that are characterised by reduced high-density lipoprotein-cholesterol (HDL-C) concentration and cholesterol efflux, and increased coronary artery disease (CAD). We explored if polymorphisms in the ABCA1 gene are associated with CAD and variations in plasma lipid levels, especially HDL-C, and whether the associations may depend on ethnicity. Male cases and controls from the Singapore Chinese, Malay and Indian populations were genotyped for five ABCA1 single nucleotide polymorphisms. Various single-locus frequency distribution differences between cases and controls were detected in different ethnic groups: the promoter -14C>T in Indians, exon 18 M883I in Malays, and 3'-untranslated (UTR) region 8994A>G in Chinese. For the Malay population, certain haplotypes carrying the I825- A (exon 17) and M883- G alleles were more frequent among cases than controls, whereas the converse was true for the alternative configuration of V825- G and I883- A, and this association was reinforced in multi-locus disequilibrium analysis that utilized genotypic data. In the healthy controls, associations were found for -14C>T genotypes with HDL-C in Chinese; 237indelG (5'UTR) with apolipoprotein A1 (apoA1) in Malays and total cholesterol (TC) in Indians; M883I with lipoprotein(a) [Lp(a)] in Malays and apolipoprotein B (apoB) in Chinese; and 8994A>G with Lp(a) in Malays, and TC, low-density lipoprotein-cholesterol (LDL-C) as well as apoB in Indians. While genotype-phenotype associations were not reproduced across populations and loci, V825I and M883I were clearly associated with CAD status in Malays with no effects on HDL-C or apoA1.     

Influence of interleukin-12 receptor β1 polymorphisms on tuberculosis

Host genetic factors may be important determinants of susceptibility to tuberculosis, and several candidate gene polymorphisms have been shown to date. A series of recent reports concerning rare human deficiencies in the type-1 cytokine pathway suggest that more subtle variants of relevant genes may also contribute to susceptibility to tuberculosis at the general population level. To investigate whether polymorphisms in the interleukin-12 receptor (IL-12R) gene predispose individuals to tuberculosis, we studied these genes by single-strand conformational polymorphism analysis and direct sequencing. Although no common polymorphisms could be identified in the IL-12R beta 2 gene ( IL-12RB2), we confirmed four single nucleotide polymorphisms (SNPs; 641A-->G, 684C-->T, 1094T-->C, and 1132G-->C) causing three missense variants (Q214R, M365T, G378R) and one synonymous substitution in the extracellular domain of the IL-12R beta 1 gene ( IL12RB1). All SNPs were in almost perfect linkage disequilibrium (D'=0.98), and two common haplotypes of IL12RB1(allele 1: Q214-M365-G378; allele 2: R214-T365-R378) were revealed. Polymerase chain reaction/restriction fragment length polymorphism and sequence analyses were used to type IL12RB1polymorphisms in 98 patients with tuberculosis and 197 healthy controls in Japanese populations. In our case-control association study of tuberculosis, the R214-T365-R378 allele (allele 2) was over-represented in patients with tuberculosis, and homozygosity for R214-T365-R378 (the 2/2 genotype) was significantly associated with tuberculosis (odds ratio: 2.45; 95% CI: 1.20-4.99; P=0.013). In healthy subjects, homozygotes for R214-T365-R378 had lower levels of IL-12-induced signaling, according to differences in cellular responses to IL-12 between two haplotypes. These data suggest that the R214-T365-R378 allele, i.e., variation in IL12RB1, contribute to tuberculosis susceptibility in the Japanese population. This genetic variation may predispose individuals to tuberculosis infection by diminishing receptor responsiveness to IL-12 and to IL-23, leading to partial dysfunction of interferon-gamma-mediated immunity.     

Endothelial nitric oxide synthase gene haplotypes and diabetic nephropathy among Asian Indians

Endothelial dysfunction plays a key role in the pathogenesis of diabetic vascular disease, including diabetic nephropathy. Endothelial-derived nitric oxide synthase (eNOS) gene polymorphisms affect eNOS activity and are associated with endothelial dysfunction. We evaluated the association of the constitutive endothelial nitric oxide synthase gene (eNOS) polymorphisms with type 2 diabetic nephropathy. We genotyped three polymorphisms of eNOS (Two SNPs: -786T > C, 894G > T and one 27-bp repeat polymorphism in Intron 4 (27VNTR)) in type 2 diabetic nephropathy patients (cases: n = 195) and type 2 diabetic without nephropathy (controls: n = 255), using validated PCR-RFLP assays. We measured serum NO levels in these subjects and examined its correlation with diabetic nephropathy and eNOS genotypes. The frequency of CC (-786T > C), TT (894G > T) and aa genotypes (27VNTR) were significantly higher in diabetic nephropathy patients as compared to the diabetes without nephropathy group (CC: P = 0.003, TT: P = 0.03, aa: P < 0.0001). These mutant genotypes were found to be associated with higher risk of nephropathy (-786T > C: OR: 5.5, 95%CI: 1.53-19.79; 894G > T: OR: 1.8, 95%CI: 1.03-3.16; Intron 4: OR: 6.23, 95%CI: 2.23-16.31). Haplotype with all the wild alleles (T-b-G) was found to be associated with a decreased risk of nephropathy (OR: 0.68, P = 0.005) and haplotype with all mutant alleles (C-a-T) was associated with higher risk of diabetic nephropathy as compared to diabetes without nephropathy group (OR: 2.6, P = 0.14). No significant linkage disequilibria were observed among the variants in this case-control study. The serum NO levels were observed to be significantly (P < 0.05) lower in mutant allele carriers ('C' allele of T-786C SNP and/or 'T' allele of G894T SNP) as compared with the wild-type allele carriers (-786T and/or 894G) within each of the subject groups (with and without nephropathy). These results suggest that the eNOS gene locus is associated with diabetic nephropathy and the functional polymorphisms (-786T > C & 894G > T) might lead to a decreased expression of eNOS gene.     

Association between the −11377 C/G and −11391 G/A polymorphisms of adiponectin gene and adiponectin levels with susceptibility to type 1 and type 2 diabetes mellitus in population from the west of Iran,correlation with lipid profile

Adipose tissue, an endocrine organ, secretes bioactive factors including adiponectin. Adiponectin is a protein hormone that enhances insulin sensitivity through increased fatty acid oxidation and inhibition of hepatic glucose production. We assessed the association of the adiponectin promoter region polymorphisms −11391 G/A and −11377 C/G with susceptibility to type 1 (T1DM) and type 2 (T2DM) diabetes mellitus in the population of west Iran. Also, we investigated the effect of adiponectin level and lipid profile on T1DM and T2DM development. In this case-control study, we recruited 189 patients with diabetes (100 T2DM and 89 T1DM) and 161 sex and age-matched unrelated healthy controls. Adiponectin mutations were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and the protein level was measured by the enzyme-linked immunosorbent assay. Other biochemical parameters were determined by routine laboratory methods. The G allele of adiponectin gene at −11377 position (C/G) significantly increased the risk of T1DM. With respect to genotype models, codominant (2.97 times), dominant (3.6-fold), and over-codominant (2.9-fold) patients with T1DM who carried −11377 C > G single-nucleotide polymorphisms were significantly susceptible to the development of the disease. A significantly higher level of adiponectin in T1DM was oberved compared with the control group. In contrast, patients with T2DM had lower adiponectin levels compared with healthy controls. The genotype distributions of −11391 G/A polymorphisms were the same for patients with diabetes and control groups. The presence of G allele at −11377 C/G adiponectin gene significantly increased serum adiponectin level and may be a risk factor for T1DM susceptibility among the western Iranian population.     

Conserved worldwide linkage disequilibrium in the human factor XI gene

We have identified, in four diverse human populations, five common single-nucleotide polymorphisms (SNPs) in the coding region of the gene for the blood coagulation protease factor XI. Each SNP has an allele frequency >5% in at least one population. Three of the SNPs (C472T, A844G, and T1234C), spread out over approximately 10 kb of genomic DNA, are in marked linkage disequilibrium (LD) with one another (P < 10(-4)). Interestingly, haplotypes associated with the linked SNPs are conserved across all populations studied, despite significantly different allele frequencies between populations. The presence of such common, widely dispersed haplotypes could complicate the interpretation of LD studies and emphasizes the need for a better understanding of general patterns of LD to facilitate identification of genes for common disorders.     

Expression and functional analyses of novel mutations of ATP-binding cassette transporter-1 in Japanese patients with high-density lipoprotein deficiency.

ATP-binding cassette transporter-1 (ABCA1) gene is mutated in patients with familial high-density lipoprotein deficiency (FHD). In order to know the molecular basis for FHD, we characterized three different ABCA1 mutations associated with FHD (G1158A/A255T, C5946T/R1851X, and A5226G/N1611D) with respect to their expression in the passaged fibroblasts from the patients and in the cells transfected with the mutated cDNAs. Fibroblasts from the all patients showed markedly decreased cholesterol efflux to apolipoprotein (apo)-Al. In the fibroblasts homozygous for G1158A/A255T, the immunoreactive mass of ABCA1 could not be detected, even when stimulated by 9-cis-retinoic acid and 22-R-hydroxycholesterol. In the fibroblasts homozygous for C5946T/R1851X, ABCA1 mRNA was comparable. Because the mutant ABCA1 protein (R1851X) was predicted to lack the epitope for the antibody used, we transfected FLAG-tagged truncated mutant (R1851X/ABCA1-FLAG) cDNA into Cos-7 cells, showing that the mutant protein expression was markedly reduced. The expression of N1611D ABCA1 protein was comparable in both fibroblasts and overexpressing cells, although cholesterol efflux from the cells was markedly reduced. These data indicated that, in the three patients investigated, the abnormalities and dysfunction of ABCA1 occurred at the different levels, providing important information about the expression, regulation, and function of ABCA1.     

五指山猪IGF2基因5′调控区单核苷酸多态性分析

利用PCR产物直接测序法, 对五指山猪、滇南小耳猪、香猪、梅山猪和大白猪共60个样本的IGF2基因5＇调控区部分片段的单核苷酸多态性进行了研究。找到13个SNP, 分别是: C5872T、C5888T、A5976G、C6010T、T6029A、C6037T、C6043T、C6063T、C6112T、C6164T、G13520A、G13563A和G13669A。T6029A为T←→A碱基颠换, A5976G、G13520A、G13563A和G13669A为A←→G转换, 其他均为C←→T转换。针对13个SNP位点得到23种组合基因型。统计各位点等位基因和基因型以及各组合基因型在总群体与各品种内的分布频率, 发现3个小型猪在A5976G、C6164T和G13669A位点上的优势等位基因均分别为G、T和A, 而梅山猪和大白猪的优势等位基因均分别为A、C和G; H19型为3个小型猪的特征组合基因型, 而另两个猪品种为H15型。同时对123头五指山猪IGF2基因C5888T位点进行了PCR-RFLP分析, 研究表明该位点C为优势等位基因(0.8536), CC为优势基因型(0.7235)。卡方检验表明该位点处于Hardy-Weinberg平衡状态。这些结果可为五指山猪等小型猪的生长发育规律、矮小机制等方面的研究提供遗传学依据。     

Association of Proopiomelanocortin Gene Polymorphisms with Obesity in the IRAS Family Study

Proopiomelanocortin (POMC) has been found to be associated with rare Mendelian forms of obesity in children, and, in linkage studies, genomic regions containing the POMC locus have been linked to leptin levels, a predictor of obesity, in white, Mexican‐American, and African‐American families. POMC polymorphisms have not been investigated in detail for association with obesity in the general population. Five single nucleotide polymorphisms (SNPs) (G‐3460C, C17T, G3473A, C3755T, and A7069G) were genotyped on 811 Hispanic individuals in the Insulin Resistance Atherosclerosis Family Study and tested for association with multiple obesity quantitative traits. General and family‐based association analyses for each individual SNP and for haplotypes were performed using the generalized estimating equation and quantitative pedigree disequilibrium test (QPDT), respectively. Modest but consistent associations were observed for SNP C3755T, with p values ranging from 0.011 to 0.045 for association with BMI, waist, visceral adipose tissue, and subcutaneous adipose tissue. G‐3460C, G3473A, and A7069G were also found to be associated with additional obesity measurements (p value 0.025 to 0.04), with comparable levels of evidence observed for linkage disequilibrium between these traits and these SNPs. Results of the haplotype analyses were also consistent with the single SNP analysis, with haplotypes containing C3755T showing the greatest evidence of association (p values ranging 0.004 to 0.048). Monte Carlo simulations (gene dropping) that account for the number of comparisons and the correlation structure indicate that the multivariate significance for these obesity traits with these polymorphisms was p = 0.0091. Collectively, the POMC polymorphisms showed consistent evidence for association with obesity traits in Hispanic Americans across several analytical approaches using SNP and haplotype analysis. These results support the hypothesis that POMC contributes genetically to the development of obesity.     

An SNP in the Adiponectin Gene Is Associated with Decreased Serum Adiponectin Levels and Risk for Impaired Glucose Tolerance

Adiponectin is a plasma protein produced by the adipose tissue. Hypoadiponectinemia has been associated with insulin resistance and several components of the metabolic syndrome (MS): type 2 diabetes, obesity, and dyslipidemia. We investigated whether single nucleotide polymorphisms (SNPs) at positions 45 and 276 in the adiponectin gene were associated with features of the MS in 747 unrelated Spanish subjects. The G allele of SNP45 and the G/G genotype of SNP276 were associated with impaired glucose tolerance (p = 0.020 and 0.042, respectively). The G/G genotype for SNP276 was associated with lower serum adiponectin levels as compared with the G/T and T/T genotypes (G/G, 10.10 ± 0.24 μg/mL; G/T, 10.98 ± 0.32 μg/mL; T/T, 12.00 ± 0.92 μg/mL; p = 0.015) even after adjustment for sex, age, BMI, waist‐to‐hip ratio, homeostasis model assessment index, and the degree of glucose tolerance (p = 0.040). We found a significant negative association of circulating adiponectin levels with waist‐to‐hip ratio (r = ?0.42, p < 0.001), sagittal abdominal diameter (r = ?0.24, p < 0.001), triglycerides (r = ?0.32, p < 0.001), homeostasis model assessment index (r = ?0.14, p = 0.001), and uric acid (r = ?0.36, p < 0.001) and positive association with high‐density lipoprotein‐cholesterol (r = 0.41, p < 0.001). Our findings indicate that serum adiponectin levels are associated with several components of the MS. The SNP276 of the adiponectin gene may affect impaired glucose tolerance and hypoadiponectinemia.     

Association of A-604G <Emphasis Type="Italic">ghrelin</Emphasis> gene polymorphism and serum ghrelin levels with the risk of obesity in a mexican population

Obesity is a metabolic disorder that has a multifactorial etiology and affects millions of people worldwide. Ghrelin, a hormone coded by the GHRL gene, plays a role in human body composition and appetite. Single nucleotide polymorphisms (SNPs) of the GHRL gene have been associated with obesity and metabolic disorders. To evaluate the association of A-604G SNP of GHRL promoter region with serum ghrelin levels and the risk of obesity in a Mexican population. Two hundred and fifty individuals were enrolled and classified as obese or control subjects (CS) according to BMI. DNA samples, anthropometric measurements and biochemical parameters were obtained from all subjects. The A-604G SNP was genotyped using PCR-RFLPs technique. Ghrelin levels were measured using a commercial enzyme immunoassay. The G/G genotype was more frequent among obese individuals (p?<?0.0001) when compared to CS. The G/A genotype and A allele were associated with protection against obesity (OR 0.29, p?<?0.0001; OR 0.39, p?<?0.0001 respectively), the A allele remained significant after adjusting for age and gender (OR: 0.25, p?<?0.0001). Serum ghrelin levels were higher in obese patients (p?=?0.004) than in CS, however, significance was lost after adjustment for age (p?=?0.088). The G/G genotype was associated with higher levels of serum ghrelin (p?=?0.02) independently of the effect of age. The G/G genotype of the A-604G SNP in the GHRL gene is associated with altered serum ghrelin levels and obesity. The A allele was also associated with protection against obesity in this study.