Association of leptin genetic polymorphism -2548 G/A with gestational diabetes mellitus

The aim of this study was to investigate possible associations of -2548 G/A polymorphism in leptin gene promoter and pregnancy-associated diseases with abnormal fetal growth such as preeclampsia and gestational diabetes. The study was also focused on whether it is rather maternal or fetal variants that determines the pathological growth status. Peripheral or cord blood samples obtained from 49 preeclamptic women and their 39 newborns, 53 healthy controls and their 53 healthy newborns and 48 patients with gestational diabetes mellitus were evaluated for leptin gene (LEP) locus -2548 genotypes. The significantly higher risk for gestational diabetes mellitus was observed in the presence of an allele (AA and AG genotypes) against carriers of GGgenotype(OR=2.84, 95%CI1.14-7.07,p=0.02). Thereisa significant risk of diabetes mellitus associated to A allele (OR=1.79, 95%CI 1.02-3.14, p=0.03). Furthermore, evaluations of preeclamptic patients' data revealed a significant association of genotype distribution and delivery and spontaneous abortion rate, where the GG carriers performed the highest pregnancy rate while the AG carriers performed the lowest spontaneous abortion rate. Our results support the hypothesis for -2548 G/A leptin gene polymorphism involvement in ethiopathogenesis of pregnancy-associated diseases with abnormal fetal growth, especially gestational diabetes mellitus.     

Leptin and leptin receptor gene polymorphisms and their association with plasma leptin levels and obesity in a multi-ethnic Malaysian suburban population

Background

This study was to investigate the prevalence of single nucleotide polymorphisms (SNPs) in leptin gene LEP (A19G and G2548A) and leptin receptor gene LEPR (K109R and Q223R) and their association with fasting plasma leptin level (PLL) and obesity in a Malaysian suburban population in Kampar, Perak.

Methods

Convenience sampling was performed with informed consents, and the study sample was drawn from patients who were patrons of the Kampar Health Clinic. A total of 408 subjects (mean age, 52.4 ± 13.7 years; 169 men, 239 women; 190 obese, 218 non-obese; 148 Malays, 177 ethnic Chinese, 83 ethnic Indians) participated. Socio-demographic data and anthropometric measurements were taken, and genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).

Results

The LEP A19G, G2548A and LEPR K109R, Q223R variant allele frequencies were 0.74, 0.67 and 0.61, 0.79, respectively. The genotype and allele distributions of these gene variants were significantly different among ethnic groups, but not among body mass index (BMI) classes. Subjects with LEPR K109 and Q223 allele had significantly higher systolic blood pressure and adiposity indices after adjustment for ethnicity (higher BMI, total body and subcutaneous fat; lower skeletal muscle percentage). Subjects with LEPR 109R allele had lower PLL than their wild-type allele counterparts. The influence of LEP A19G and G2548A SNPs on blood pressures, anthropometrics, and PLL was not evident. Interestingly, synergistic effect of the LEP and LEPR SNPs was observed as subjects homozygous for all four SNPs studied exhibited significantly higher subcutaneous fat and PLL than those with other genotype combinations.

Conclusions

The LEP and LEPR SNPs in this study may not be an obesity marker among Malaysians in this population, but were associated with ethnicity. Our findings suggest that each of these SNPs contributes to minor but significant variation in obesity-related traits and in combination they display synergistic effects on subcutaneous fat and PLL.     

The Q223R polymorphism in LEPR is associated with obesity in Pacific Islanders

Various Pacific Island populations have experienced a marked increase in the prevalence of obesity in past decades. This study examined the association of a promoter polymorphism of the leptin gene (LEP), G-2548A (rs7799039), and two non-synonymous single nucleotide polymorphisms of the leptin receptor gene (LEPR), K109R (rs1137100) and Q223R (rs1137101), with body weight, body mass index (BMI) and obesity (BMI ≥ 30) in Pacific Islanders. A total of 745 Austronesian (AN)-speaking participants were analyzed after adjusting for age, gender, and population differences. The results revealed that carriers of the 223Q alleles of LEPR had significantly higher body weight (P = 0.0009) and BMI (P = 0.0022) than non-carriers (i.e., 223R homozygotes); furthermore, the 223Q carriers also had a significantly higher risk of obesity in comparison to non-carriers (P = 0.0222). The other two polymorphisms, G-2548A and K109R, were associated with neither body weight, BMI, nor obesity. The 223Q allele was widely found among the AN-speaking study subjects, thus suggesting that the LEPR Q223R polymorphism is one of the factors contributing to the high prevalence of obesity in the Pacific Island populations.     

Leptin expression and leptin receptor gene polymorphisms in growth hormone deficiency patients

Growth hormone deficiency (GHD) patients have lower weight, height, bone age, insulin-like growth factor 1 (IGF-1) levels, GH levels, fat metabolism and skeletal growth. The association of leptin with GHD characteristics and the effect of gene variants of leptin on GHD are unknown. Our aim was to examine the association of circulating leptin levels and common genetic variants in leptin (LEP) and leptin receptor (LEPR) genes with anthropometric measures, circulating hormone concentrations and GHD. A case control study of 125 GHD cases and 159 control subjects were characterized for bone age, body mass index (BMI), height, weight, leptin, IGF-1, GH and their genotype at the leptin promoter G-2548A, and LEPR variants, K109R and Q223R, at Chung Shan Medical University Hospital. Leptin levels were significantly associated with lower bone age, weight and BMI in GHD patients. Leptin levels were also significantly associated with reduced IGF-1 levels in girls but not boys in both groups. The frequency of LEPR223 [A/G or A/A] genotype was significantly higher than the LEPR223 G/G genotype in the GHD group. The LEPR223 [A/G or A/A] genotype was significantly associated with increased weight and BMI in the control group, but not in the GHD group. In conclusion, the GHD group carried a significantly higher frequency of the LEPR [G/A or A/A] genotype and of the A allele (LEPR223R). The LEPR223R polymorphism affected weight and BMI in control, but not in GHD patients, suggesting that the effect of LEPR223 [A/G or A/A] genotype was counteracted by other factor(s) in GHD patients.     

Effects of β2‐Adrenergic Receptor Gene Variants on Adiposity: The HERITAGE Family Study

We investigated whether the Arg16Gly and Gln27Glu polymorphisms of the β2‐adrenergic receptor gene were associated with body‐fat and fat‐distribution phenotypes measured before and in response to a 20‐week endurance‐training program. BMI, fat mass (FAT), percentage of body fat (%FAT), sum of eight skinfolds (SF8), and abdominal fat areas assessed by computed tomography were measured in adult sedentary white and black participants of the HERITAGE Family Study. Evidence of gene‐by‐obesity interaction was found in whites for several adiposity phenotypes measured before training. Analyses performed separately in nonobese and obese subjects revealed that obese men carrying the Glu27 allele have lower fat accumulation (BMI, FAT, and %FAT) than noncarriers. Among white obese women, Gly16Gly homozygotes had a lower fat accumulation (BMI, FAT, and SF8) than Arg16Gly and Arg16Arg carriers. In response to endurance training, white women with the Arg16Arg genotype exhibited a greater reduction in BMI, FAT, and %FAT. Results observed in blacks were mostly negative. These results suggest that polymorphisms in the β2‐adrenergic receptor gene influence the amount of body fat in white obese men (Gln27Glu) and women (Arg16Gly), as well as the changes in adiposity in response to endurance training in white women (Arg16Gly).     

G-2548A polymorphism of the leptin gene is correlated with extreme obesity in Taiwanese aborigines

We examined the genetic associations of the G-2548A polymorphism in the promoter of the leptin (LEP) gene and the Gln223Arg (Q223R) polymorphism of the leptin receptor (LEPR) gene with obesity. Two hundred twenty-six obese aboriginal subjects (BMI > or = 27 kg/m2) and 182 aboriginal subjects with normal weight (BMI < 25 kg/m2) participated in this study. The polymorphisms of LEP G-2548A and LEPR Q223R were genotyped by polymerase chain reaction/restriction fragment length polymorphism, and their anthropometric characteristics were measured. Levels of leptin, triglycerides, and cholesterol were measured after overnight fasting. We found that the frequencies of the LEP G/G homozygote (22.6%) with Mendelian recessive (chi2 = 7.89, p = 0.005) and codominant (chi2 = 7.93, p = 0.02) models to be higher in the extremely obese subjects (BMI > or = 35 kg/m2) than in normal weight subjects (6.9%) but not in moderately obese subjects (35 > BMI > or = 27 kg/m2). There was no difference in genotypic frequency of the LEPR Q223R polymorphism between the extreme obese and control groups. We suggest that the LEP -2548 G/G homozygote plays a genetic recessive role in the development of extreme obesity in Taiwanese aborigines.     

Leptin promoter variant G2548A is associated with serum leptin and HDL-C levels in a case control observational study in association with obesity in a Pakistani cohort

Leptin is a protein hormone synthesized by adipocytes and is involved in the regulation of food intake and energy expenditure. We hypothesized that any change in the promoter sequence can affect the expression of the gene and hence leptin protein levels in the serum. The aim of the current study was to investigate the relationship of such a promoter variant of the leptin gene, G-2548A polymorphism, with obesity and its effect on various anthropometric and metabolic parameters in a Pakistani cohort consisting of 250 obese and 225 non-obese control subjects. Body weight, height, waist circumference (WC), hip circumference (HC) and blood pressure (BP) were measured by standard methods and levels of fasting blood glucose (FBG), total cholesterol, triglycerides, HDLC, LDLC, and leptin were determined. Genotyping was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The results showed that the LEP G-2548A polymorphism showed significant association with obesity in Pakistan. In addition, the polymorphism showed association with weight, height, BMI, WC, HDLC and serum leptin levels. The findings suggest that the leptin promoter G-2548A variant may play its part in the progression to obesity by not only affecting the body’s fat distribution but also by changing the serum leptin and HDLC levels.     

间歇性低氧对肥胖小鼠瘦素及其受体表达的影响

为探讨适度低氧环境对体重的影响及其作用机制,明确瘦素在其中的作用,用高脂饮食建立小鼠肥胖模型并观察间歇性低氧的干预效果。健康昆明小鼠随机分为4组（每组20只）,正常对照组：喂正常食物,不进行间歇性低氧训练;低氧组：喂正常食物,并进行间歇性低氧训练;肥胖组：喂高脂、高糖食物,但不进行间歇性低氧训练;低氧＋肥胖组,喂高脂、高糖食物,并进行间歇性低氧训练。40d后,测量小鼠体重,用酶联免疫吸附法测定血清瘦素水平,免疫组织化学检测肝脏瘦素受体表达,苏丹Ⅲ染色检测肝脏脂肪细胞分布和密度。结果显示,与正常对照组相比,肥胖组小鼠平均体重和平均血清瘦素水平显著升高,肝脏分布大量脂肪细胞,提示高脂模型建立成功;经过间歇性低氧训练后,低氧组和低氧＋肥胖组小鼠的平均体重及肝脏脂肪细胞分布密度和范围分别较对照组和肥胖组低,而血清瘦素水平明显增高;低氧＋肥胖组小鼠肝脏瘦素受体的表达高于肥胖组。结果提示,适度的间歇性低氧可以通过提高血清瘦素水平和增强肝脏瘦素受体表达而使体重减轻,并有效防止肝细胞脂肪变。     

Leptin G-2548A and leptin receptor Q223R gene polymorphisms are not associated with obesity in Romanian subjects

We aimed to investigate whether polymorphisms LEP G-2548A and LEPR Q223R in the human leptin (LEP), and leptin receptor (LEPR) genes are associated with obesity and metabolic traits in a sample of Romanian population. Two hundred and two subjects divided in obese (body mass index, BMI ? 30 kg/m²), and non-obese were included in this study. The polymorphisms were genotyped using polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP) analysis. The results showed no significant differences in LEP and LEPR genotype and allele frequencies between obese and non-obese subjects. Logistic regression analysis showed that LEP -2548GG genotype presented an increased risk of obesity (p = 0.013, OR = 1.003, 95% CI = 1.000-1.007), after adjusting for age and gender. The association analysis with metabolic syndrome quantitative traits showed that homozygous for LEP -2548G allele had significantly higher leptin levels (17.2 ± 6.6 ng/ml vs. 13.2 ± 4.9 ng/ml, p = 0.011), and carriers of R allele had higher levels of triglycerides (p = 0.017) and glucose (p = 0.040), and enhanced systolic (p = 0.015) and diastolic blood pressure (p = 0.026), after adjustment for age, gender, and BMI. These results indicate that LEP G-2548A and LEPR Q223R SNPs may not be considered as genetic risk factors for obesity in a sample of Romanian population. However, LEP -2548GG genotype appear to be important in regulating leptin levels, whereas the LEPR 223R allele might predispose healthy subjects to develop metabolic disturbances.     

LEPR p.Q223R, beta3-AR p.W64R and LEP c.-2548G>A gene variants in obese Brazilian subjects

Obesity is due to the combined effects of genes, environment, lifestyle, and the interactions of these factors. The adrenergic receptor beta3 (beta3-AR), leptin (LEP) and leptin receptor (LEPR) genes have been intensively evaluated in the search of variants that could be related to obesity and its cardiometabolic complications. The results of most of these studies have been controversial. In the present study, we investigated the relationship of the beta3-AR p.W64R, LEP c.-2548G>A and LEPR p.Q223R gene variants with body mass index (BMI), in Brazilian subjects of different genetic backgrounds and ethnic origins. Two hundred obese patients (60 males, 140 females, BMI > or = 30 kg/m2) were screened and compared to 150 lean healthy subjects (63 males, 87 females, BMI < or = 24 kg/m2). Genomic DNA was extracted and amplified by polymerase chain reaction. Polymerase chain reaction products were digested with specific restriction enzymes and separated by electrophoresis. There was no significant difference in the genotype frequency of the beta3-AR p.W64R and the LEP c.-2548G>A polymorphisms, between lean and obese subjects. However, the genotype and allele frequencies of the LEPR p.Q223R variant were significantly different between the normal weight and obese groups. Haplotype analysis has shown an association between the G/G allelic combination of c.-2548G>A LEP and c.668A>G LEPR, in obese subjects. Our results suggest that genetic variability in the leptin receptor is associated with body weight regulation, the LEPR p.Q223R variant being related to BMI increase. The haplotype combination of LEP c.-2548G>A and LEPR p.Q223R variants was related to a 58% increase in obesity risk.     

Functional polymorphism of the mu-opioid receptor gene (OPRM1) influences reinforcement learning in humans

Previous reports on the functional effects (i.e., gain or loss of function), and phenotypic outcomes (e.g., changes in addiction vulnerability and stress response) of a commonly occurring functional single nucleotide polymorphism (SNP) of the mu-opioid receptor (OPRM1 A118G) have been inconsistent. Here we examine the effect of this polymorphism on implicit reward learning. We used a probabilistic signal detection task to determine whether this polymorphism impacts response bias to monetary reward in 63 healthy adult subjects: 51 AA homozygotes and 12 G allele carriers. OPRM1 AA homozygotes exhibited typical responding to the rewarded response--that is, their bias to the rewarded stimulus increased over time. However, OPRM1 G allele carriers exhibited a decline in response to the rewarded stimulus compared to the AA homozygotes. These results extend previous reports on the heritability of performance on this task by implicating a specific polymorphism. Through comparison with other studies using this task, we suggest a possible mechanism by which the OPRM1 polymorphism may confer reduced response to natural reward through a dopamine-mediated decrease during positive reinforcement learning.     

FTO Genotype Is Associated With Exercise Training–induced Changes in Body Composition

The fat mass (FM) and obesity‐associated (FTO) gene is the first obesity‐susceptibility gene identified by genome‐wide association scans and confirmed in several follow‐up studies. Homozygotes for the risk allele (A/A) have 1.67 times greater risk of obesity than those who do not have the allele. However, it is not known whether regular exercise‐induced changes in body composition are influenced by the FTO genotype. The purpose of our study was to test whether the FTO genotype is associated with exercise‐induced changes in adiposity. Body composition was derived from underwater weighing before and after a 20‐week endurance training program in 481 previously sedentary white subjects of the HERITAGE Family Study. FTO single‐nucleotide polymorphism (SNP) rs8050136 was genotyped using Illumina GoldenGate assay. In the sedentary state, the A/A homozygotes were significantly heavier and fatter than the heterozygotes and the C/C homozygotes in men (P = 0.004) but not in women (P = 0.331; gene‐by‐sex interaction P = 0.0053). The FTO genotype was associated with body fat responses to regular exercise (P < 0.005; adjusted for age, sex, and baseline value of response trait): carriers of the C allele showed three times greater FM and %body fat losses than the A/A homozygotes. The FTO genotype explained 2% of the variance in adiposity changes. Our data suggest that the FTO obesity‐susceptibility genotype influences the body fat responses to regular exercise. Resistance to exercise‐induced reduction in total adiposity may represent one mechanism by which the FTO A allele promotes overweight and obesity.     

Lower serum leptin concentrations in rugby players in comparison with healthy non-sporting subjects--relationships to anthropometric and biochemical parameters

Leptin is a protein hormone synthesized by adipocytes. Its serum concentrations reflect the total body fat content. Serum leptin concentrations are significantly higher in obese than in lean people and in women than in men. However little information about the influence of physical activity on serum leptin concentrations is available. We have compared the body weight, the body mass index (BMI), the body fat content (measured by caliper as skinfold thickness) and the serum concentrations of leptin, triglycerides, total, high density and low density lipoprotein (LDL) cholesterol in 14 top rugby players and 10 healthy controls. We found that serum leptin, total and LDL cholesterol concentrations were significantly lower in the rugby players group than in the control subjects. The body weight and BMI were significantly higher in the rugby players, while the body fat content was only slightly (non-significantly) higher in the control group. The serum leptin concentrations in both groups positively correlated with the BMI and body fat content and also with LDL concentrations in the control group. The serum leptin concentrations in the rugby players were lower than in the non-sporting subjects despite a similar body fat content in both groups. We would therefore suggest the possibility that regular hard physical training decreases serum leptin concentrations not only by the decrease of total body fat content, but also by a separate mechanism, which is not directly dependent on the changes in the amount of body adipose tissue.     

Differential effects of the C1431T and Pro12Ala PPARgamma gene variants on plasma lipids and diabetes risk in an Asian population

We investigated the association of C1431T and Pro12Ala polymorphisms at the peroxisome proliferator-activated receptor gamma (PPARgamma) locus with plasma lipids and insulin resistance-related variables, according to diabetes status, in a large and representative Asian population from Singapore consisting of 2,730 Chinese, 740 Malays, and 568 Indians. Moreover, we estimated the diabetes risk and examined gene-nutrient interactions between these variants and the ratio of polyunsaturated fatty acid to saturated fat (SFA) in determining body mass index (BMI) and fasting insulin. We found differential effects of these gene variants. The Pro12Ala polymorphism was more associated with plasma lipids and fasting glucose concentrations, whereas the C1431T polymorphism was related to the risk of diabetes. Carriers of the 12Ala allele had higher HDL-cholesterol than did Pro12Pro homozygotes (P < 0.05), and the effect of the 12Ala allele on fasting glucose was modified by diabetes status (P < 0.001). After controlling for confounders, carriers of the T allele had decreased risk of diabetes compared with CC homozygotes [odds ratio (OR) 0.73, 95% confidence interval (CI) 0.58-0.93; P = 0.011]; this effect was stronger in Indians (OR 0.38, 95% CI 0.15-0.92; P = 0.032). For both polymorphisms, normal subjects carrying the less prevalent allele had higher BMI (P < 0.05). The PUFA/SFA did not modify the effect of these polymorphisms on BMI or insulin.     

ACDC/Adiponectin and PPAR‐γ Gene Polymorphisms: Implications for Features of Obesity

Objective: The main purpose of this study was to investigate associations of single‐nucleotide polymorphisms (SNPs) in the adipocyte C1q and collagen domain‐containing (ACDC) gene and its regulator, the nuclear peroxisome proliferator‐activated receptor (PPAR)‐γ gene, with body fat mass and its topographical distribution in postmenopausal women. Research Methods and Procedures: Participants were 1501 healthy women, 60 to 85 years old, who were genotyped for four SNPs in the ACDC gene (−11391G/A, −11377C/G, +45T/G, +276G/T) and the Pro12Ala SNP in the PPAR‐γ gene. Total body fat mass and the central to peripheral fat mass ratio (CFM/PFM ratio) were measured using DXA. Adiponectin and homeostasis model assessment of insulin resistance were measured in 287 subjects. Results: The −11377C/G SNP was associated with adiponectin (p < 0.001) and the CFM/PFM ratio (p = 0.005); the G allele being associated with low adiponectin and high CFM/PFM ratio. Similar associations of adiponectin (p = 0.0001) and the CFM/PFM ratio (p = 0.002) characterized the 1_2 (G_G) promoter haplotype (11391G/A_−11377C/G). Genotype variation of SNP Pro12Ala was associated with total body fat mass (p = 0.04); women with GG being the most obese (p = 0.01). The Ala/Ala (GG) genotype of Pro12Ala SNP interacted with the CC genotype of SNP‐11377C/G in the determination of BMI (p = 0.001), when analyzed using a codominant model. Discussion: Polymorphisms in the ACDC gene are associated with body fat distribution, whereas the Pro12Ala polymorphism in PPAR‐γ is associated with overall adiposity, apparently in interaction with an ACDC promoter SNP.     

Leptin −2548 G/A polymorphisms are associated to clinical progression of oral cancer and sensitive to oral tumorization in nonsmoking population

Oral cancer is causally associated with environmental carcinogens, and the susceptibility to carcinogen-mediated tumorigenesis is proposed to be genotype-dependent. Leptin (LEP) and leptin receptor (LEPR) both play a crucial role in the mediation of physiological reactions and carcinogenesis and may serve as a candidate biomarker of oral cancer. The current case-control study aimed to examine the effects of LEP −2548 G/A (rs7799039), LEPR K109R (rs1137100), and LEPR Q223R (rs1137101) single-nucleotide polymorphisms (SNPs) with or without interacting to environmental carcinogens on the risk for oral squamous cell carcinoma. The SNPs of three genetic allele, from 567 patients with oral cancer and 560 healthy controls in Taiwan were analyzed. The results shown that the patients with polymorphic allele of LEP −2548 have a significant low risk for the development of clinical stage (A/G: adjusted odds ratio [AOR] = 0.670, 95% confidence interval [CI] = 0.454-0.988, P < 0.05; A/G + G/G: AOR = 0.676, 95% CI = 0.467-0.978, P < 0.05) compared to patients with ancestral homozygous A/A genotype. In addition, an interesting result was found that the impact of LEP −2548 G/A SNP on oral carcinogenesis in subjects without tobacco consumption is higher than subjects with tobacco consumption. These results suggest that the genetic polymorphism of LEP −2548 G/A (rs7799039), LEPR K109R (rs1137100), and LEPR Q223R (rs1137101) were not associated to the susceptibility of oral cancer; SNP in LEP −2548 G/A showed a poor clinicopathological development of oral cancer; population without tobacco consumption and with polymorphic LEP −2548 G/A gene may significantly increase the risk to have oral cancer.     

Leptin, superoxide dismutase, and weight loss: initial leptin predicts weight loss

Objective: Our goal was to study how plasma leptin concentration, superoxide dismutase (SOD) activity, and weight loss are related in obese adults. Research Methods and Procedures: Serum leptin concentration, SOD activities, general biochemical data, and body composition measurements were obtained for 62 overweight and obese subjects before and after an 8‐week body weight reduction (BWR) regimen. The subjects were on dietary control, performed moderate aerobic and strength training exercises, and attended educational lectures. Results: The measurement results indicated that the following criteria were significantly reduced: body weight [84.4 ± 17.0 vs. 79.3 ± 16.1 (standard error) kg, p < 0.001]; BMI (31.5 ± 4.3 vs. 29.4 ± 4.2 kg/m², p < 0.001), and fat mass (33.3 ± 10.0 vs. 29.8 ± 10.4 kg, p < 0.001). Plasma leptin levels also significantly decreased from 31.5 ± 17.6 to 26.5 ± 17.2 ng/mL (p < 0.001). Additionally, SOD activity was significantly increased from 261.4 ± 66.0 to 302.7 ± 30.9 U/mL (p < 0.001). Based on linear regression analysis results, a 3.78‐ to 8.13‐kg reduction in weight can be expected after the 8‐week BWR regimen when initial leptin concentration was 5 to 30 ng/mL. Discussion: We found that an 8‐week exercise and diet program was effective in reducing weight and fat mass and, notably, had further beneficial effects on leptin resistance and SOD activity. Additionally, this study demonstrated that initial plasma leptin concentration may be used as a predictor for weight loss outcome.     

Association of adiponectin promoter variants with traits and clusters of metabolic syndrome in Arabs: Family-based study

Plasma levels of adiponectin are decreased in type 2 diabetes, obesity and hypertension. Our aim was to use a family-based analysis to identify the genetic variants of the adiponectin (ADIPOQ) gene that are associated with obesity, insulin resistance, dyslipidemia and hypertension, among Arabs. We screened 328 Arabs in one large extended family for single nucleotide polymorphisms (SNPs) in the promoter region of the ADIPOQ gene. Two common SNPs were detected: rs17300539 and rs266729. Evidences of association between traits related to the metabolic syndrome and the SNPs were studied by implementing quantitative genetic association analysis. Results showed that SNP rs266729 was significantly associated with body weight (p-value = 0.001), waist circumference (p-value = 0.037), BMI (p-value = 0.015) and percentage of total body fat (p-value = 0.003). Up to 4.1% of heritability of obesity traits was explained by the rs266729 locus. Further cross-sectional analysis showed that carriers of the G allele had significantly higher values of waist circumference, BMI and percentage of total body fat (p-values 0.014, 0.004 and 0.032, respectively). No association was detected between SNP rs266729 and other clusters of metabolic syndrome or their traits except for HOMA-IR and fasting plasma insulin levels, p-values 0.035 and 0.004, respectively. In contrast, both measured genotype and cross-sectional analysis failed to detect an association between the SNP rs17300539 with traits and clusters of metabolic syndrome. In conclusion, we showed family-based evidence of association of SNP rs266729 at ADIPOQ gene with traits defining obesity in Arab population. This is important for future prediction and prevention of obesity in population where obesity is in an increasing trend.