Obesity-related Gene Polymorphisms Research Articles

A profile of body composition and obesity related gene polymorphism among eastern and north eastern populations of India

BackgroundBody composition and obesity is one of the major health related risk factors leading to increased metabolic mortality and morbidity. The Association of genetic polymorphism with obesity and body composition is one way to assess the health status of a given population. In Indian region of east and north east, population-based studies have been conducted to assess the relation of body composition and obesity with gene polymorphism known to be associated with obesity and cardiovascular health and disease. MethodsThe current study consisted of different ethnic groups of Eastern and North Eastern part of India. A total of 225 randomly selected apparently healthy unrelated (free from any major diseases) adult individuals of 12 Ethnic groups were selected for the present study. Kurmi, Bhumij and Bouri population of Purulia District, and Bengali population of Kolkata, West Bengal, Meitei population of Manipur, Kolui, Riang, Rupini, Chakma and Tripuri of Tripura, Santal and Sabar population of Jharkhand, India were incorporated in the present study. FTO, ACE3, PSD3 and A604G genotyping by Restriction Fragment length Polymorphism (RFLP) was performed to study specific Single Nucleotide Polymorphism (SNP) among the population. Anthropometric and socio demographic data were collected from all the subjects as per standard procedure. Overweight and obese categories for BMI classification was determined using classifications based on BMI, WC, WHR, WSR and BF percentage. ResultsThe genetic polymorphism studied showed no significant relation among any of the 4 gene polymorphism with body composition variables. Smaller insignificant fraction of polymorphism for ACE, FTO gene was observed in population 3. PSD3 and A604G and polymorphism was not observed in any of the population studied. ConclusionComparison of the results from anthropometric, physiological, metabolic data on the basis of body composition and gene polymorphism indicated that the studied population of twelve ethnic groups might not be susceptible to ACE, FTO, PSD3 and A604G associated obesity related disease.

Polikistik Over Sendromu ve Obezite: FTO ve MC4R Gen Polimorfizmlerinin Rolü

Polikistik Over Sendromu (PKOS) etiyolojisi karmaşık olan multifaktöriyel bir endokrin bozukluktur. Ayrıca kadınlarda obezite ve tip 2 diyabet gelişim riskini arttıran metabolik bozukluklarla da ilişkilidir. Obezite/adipozite ve insülin direnci PKOS’lu kadınlarda oldukça sık karşılaşılan bir problemdir. İnsan genomunun ayrıntılı olarak incelendiği genom projelerinde obezite ve bazı hastalıklarla ilişkili çok sayıda gen ve genetik varyasyonların bulunduğu gösterilmiştir. Bu genler içerisinde yağ kütlesi ve obezite ile ilişkili gen (FTO) ve melanokortin-4 reseptör geni (MC4R) varyantları obezite, aşırı vücut ağırlığı ve tip 2 diyabet ile ilişkilidir. Bu nedenle FTO ve MC4R genlerinin obezite/adipozite gelişimine etkileri yoluyla PKOS ile ilişkili olabileceği öne sürülmektedir. Bu derleme makalede obeziteyle ilişkili bazı gen polimorfizmlerinin (FTO ve MC4R) PKOS ile ilişkisi incelenmiştir.

Interactions among insulin resistance, inflammation factors, obesity-related gene polymorphisms, environmental risk factors, and diet in the development of gestational diabetes mellitus

Purpose: The aim of this study was to investigate the correlations and interactions between the polymorphisms of insulin resistance-related genes (ADIPOQ rs2241766), inflammation factors (TNF-α rs1800629, IL-6 rs1800795), obesity-related genes (GNB3 rs5443, ADRB rs1042714), and risk factors for gestational diabetes mellitus (GDM) such as diet structure in the development of GDM.Materials and methods: This research was conducted among women who visited the third-affiliate hospital of Zhengzhou University for pregnancy checkups from 1 June 2014 to 30 December 2014. Based on the results of a 75-g glucose tolerance test (OGTT), 140 pregnant women with GDM were randomly selected as a part of the GDM group and140 healthy, pregnant women as part of the control group. Relevant clinical and laboratory data for the child and the mother including her pregnancy outcomes and the delivery mode were collected for the epidemiological survey.Results: The results showed that risk factors for GDM are advanced age, the hepatitis B virus, family history of diabetes, high body mass index before pregnancy, and weight gain of ≥10 kg before 24-week gestation. We found that diet structures were severely unbalanced. The polymorphisms rs2241766 and rs5443 were found to potentially be associated with GDM; moreover, a positive interaction was demonstrated between rs2241766 and age, and a negative interaction was demonstrated with weight gain of ≥10 kg before 24-week gestation.Conclusion: Our findings demonstrate that both environmental risk factors and genetic background contribute to the development of GDM.

Association of two obesity-related gene polymorphisms LEPG2548A rs7799039 and LEPRQ223R rs1137101 with the risk of breast cancer.

Many studies have been performed to investigate the correlation of leptin (LEP) and leptin receptor (LEPR) polymorphisms with breast cancer (BC) risk, however the results are inconclusive. To obtain a more precise estimation, we conducted this meta-analysis. We searched PubMed, EMBASE, and Web of Science databases to identify qualified studies. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the association. Eight eligible studies (2,124 cases and 5,476 controls) for LEP G2548A (rs7799039) polymorphism, and thirteen studies (5,282 cases and 6,140 controls) for LEPR Q223R (rs1137101) polymorphism were included in our study. In general, no significant association between LEP G2548A polymorphism and BC susceptibility was found among five genetic models. In the stratified analysis by ethnicity and sources of controls, significant associations were still not detected in all genetic models. For LEPR Q223R polymorphism, we observed that the association was only statistically significant in Asians (G versus A: OR = 0.532, P = 0.009; GG versus AA: OR = 0.233, P = 0.002; GA versus AA: OR =0.294, P = 0.006; GG versus AA+AG: OR =0.635, P = 0; GA+GG versus AA: OR = 0.242, P = 0.003), but not in general populations and Caucasians. In conclusion, LEP G2548A polymorphism has no relationship with BC susceptibility, while LEPR Q223R polymorphism could decrease BC risk in Asians, but not in overall individuals and Caucasians. More multicenter studies with larger sample sizes are required for further investigation.

Possible relationship between the resistin gene C-420G polymorphism and colorectal cancer in a Turkish population.

In recent years, with improvements in genotyping, a possible relationship between obesity-related gene polymorphisms and colorectal cancer (CRC) has been studied. The promoter region C-420G of the resistin gene is believed to have an important role in the development of malignancy. We prospectively evaluated the possible effect of the resistin C-420G polymorphism on the risk and prognosis of CRC. One hundred twenty-three patients with CRC and 79 healthy individuals were included in the study. Blood samples were genotyped, and the relationship between the resistin C-420G polymorphism and demographic characteristics and tumor features was evaluated. No statistically significant difference was found in genotype distribution between the patient and control groups and among patients in the means of gender, biochemical findings, and tumor characteristics (p>0.05). The relationship between the C-420G polymorphism and various diseases has been evaluated in many studies to date. With the increased importance of obesity in etiopathogenesis, studies have focused on CRC. According to our results, the GG genotype may be associated with a decreased CRC risk. Our study is important because to our knowledge, it is the first one to be conducted in a Turkish population to date, but we believe that more patients and controls are needed to obtain statistically significant results.

Correlations among obesity-associated gene polymorphisms, body composition, and physical activity in patients with type 2 diabetes mellitus.

Context:Various studies have focused on the correlation between β2-adrenergic receptor (β2AR), the β3-adrenergic receptor (β3AR), and the uncoupling protein 1 (UCP1) polymorphisms and obesity in patients with type 2 diabetes mellitus (T2DM).Aims:We examined the correlation between these polymorphisms and body composition variables and between body composition and lifestyle variables in Japanese T2DM patients.Materials and Methods:Of the 48, T2DM outpatients in Kanagawa prefecture recruited for participation, 32 (6 men and 26 women) met the study criteria and were enrolled. Obesity-related gene polymorphisms were identified in 3 genes β3AR, UCP1, and β2AR using the SMart amplification process. Body composition variables were measured using a body composition analyzer. Data regarding food and nutrient consumption, family history, and lifestyle factors were collected via administration of questionnaires.Results:Because significant differences in body composition variables were found between men and women, statistical analysis was performed with data from the 25 female subjects only. On the basis of results of genetic testing, the subjects were divided into genotype groups for two-group and three-group comparison. The β3AR, UCP1, and β2AR polymorphisms and body composition significantly correlated with the percentage of subcutaneous fat in both arms as compared with the wild type or hetero groups with β3AR polymorphisms. However, physical activity correlated with several body composition variables.Conclusions:These results suggest that obesity in T2DM patients is not the result of presence of an obesity-related gene polymorphism but rather the absence of daily physical activity.

Impact of obesity-related gene polymorphism on risk of obesity and metabolic disorder in childhood

To examine the impact of single nucleotide polymorphisms in obesity-related genes on risk of obesity and metabolic disorder in childhood. A total of 3 503 Chinese children aged 6 to 18 years participated in the study, including 1 229 obese, 655 overweight and 1 619 normal weight children (diagnosed by the Chinese age- and sex- specific BMI cutoffs). Body size parameters were assessed and venipuncture blood samples were collected after a 12-hour overnight fast. Plasma glucose, insulin and serum lipid profiles were measured.Genomic DNA was isolated from peripheral blood white cells using the salt fractionation method. A total of 11 single nucleotide polymorphisms were genotyped by TaqMan allelic discrimination assays with the GeneAmp 7900 sequence detection system (Applied Biosystems, Foster City, CA, USA) (FTO rs9939609, MC4R rs17782313, GNPDA2 rs10938397, FAIM2 rs7138803, BDNF rs6265, NPC1 rs1805081, PCSK1 rs6235, KCTD15 rs29941, BAT2 rs2844479, SEC16B rs10913469 and SH2B1 rs4788102). Multiple factor analysis was performed to estimate the association between the variant and obesity-related traits. The false discovery rate (FDR) approach was used to correct for multiple comparisons. After sex, age and pubertal stage adjustment and correction for multiple testing, the rs9939609-A, rs17782313-C, rs10938397-G, and rs7138803-A alleles were associated with higher BMI (β = 0.352-0.747), fat mass percentage(β = 0.568-1.113), waist circumference (β = 0.885-1.649) and waist-to-height ratio(β = 0.005-0.010) (all P values < 0.01) in Chinese children. The rs6265-G allele increased BMI(β = 0.251, P = 0.020). The rs9939609-A, rs17782313-C, and rs10938397-G and rs6265-G alleles were also associated with risk of obesity (OR = 1.386, 95%CI:1.171-1.642; OR = 1.367, 95%CI:1.196-1.563; OR = 1.242, 95%CI:1.102-1.400; OR = 1.156, 95%CI:1.031-1.296).Rs7138803 was associated with risk of obesity only in boys (OR = 1.234, 95%CI:1.043-1.460). GNPDA2 rs10938397-G allele was associated with risk of insulin resistance(OR = 1.205, 95%CI:1.069-1.359), but there was no significance after adjusting for BMI. The association of FTO rs9939609-A, MC4R rs17782313-C, GNPDA2 rs10938397-G, and FAIM2 rs7138803-A with higher BMI, fat mass percentage, waist circumference, and waist-to height ratio and risk of obesity, and BDNF rs6265-G allele may increase BMI and obesity risk in Chinese children. GNPDA2 rs10938397-G may increase the risk of childhood insulin resistance depending on BMI.

Risk of obesity-related gene polymorphism on the incidence and durative of childhood obesity

To examine the impact of single nucleotide polymorphisms(SNPs)in obesity-related genes on the incidence and durative of obesity in childhood and adolescence. Based on the Beijing Child and Adolescent Metabolic Syndrome (BCAMS) Study, 780 school children aged 6 to 16 years were followed-up in 2010, and assessed for body size parameters. Venipuncture blood samples were collected after a 12-hour overnight fast. Genomic DNA was isolated from peripheral blood white cells under the salt fractionation method. SNPs were genotyped by ABI 5700 real time PCR(FTO rs9939609)and TaqMan Allelic Discrimination Assays with the GeneAmp 7900 Sequence Detection System(Applied Biosystems,Foster City, CA, USA) (FTO rs6499640, FAIM2 rs7138803,NPC1 rs1805081, MC4R rs17782313, BDNF rs6265, GNPDA2 rs10938397). Both overweight and obesity were diagnosed by the Chinese age- and sex- specific body mass index(BMI) cutoffs. Two independent sample t-test, Chi-square test and multiple logistic regression analysis were performed. During the 6 years follow-up period, the incidence of obesity in the total sample 8.5%, and 65.1% individuals had persisted their obese status. The genotypes of the SNPs except BDNF rs6265 were in Hardy-Weinberg equilibrium in each group (P > 0.05). The incidence rates of obesity increased with FTO rs9939609 TT,TA and AA genotypes(χ(2) for trend = 8.030, P < 0.05). In the non-obese sub-cohort, after adjusted for sex, age at the initial time of follow up and residential area, when compared with children carrying FTO rs9939609 T-allele, a significantly relative risk of obesity was observed for children carrying the rs9939609 A-allele(OR = 2.42, 95%CI:1.31-4.47, P = 0.005). In the obese sub-cohort, FTO rs9939609 A-allele was significantly associated with durative of obesity (OR = 1.72, 95%CI:1.07-2.77, P = 0.026). However, no statistical significant associations were seen between other SNPs(FTO rs6499640, FAIM2 rs7138803, NPC1 rs1805081, MC4R rs17782313, GNPDA2 rs10938397)and the incidence or durative of obesity(all P > 0.05). The genetic risk score was associated with the risk of occurrence of obesity(OR = 16.42, 95% CI:3.59-75.10, P < 0.001) after adjusted for residential area, sex, age at the initial time of follow up and baseline BMI. We confirmed the association of FTO rs9939609 with incidence and durative of obesity in children. Early intervention was recommended on the high risk individuals who carrying more risk alleles in obesity-related genes.