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Common Genetic Variant of insig2 Gene rs7566605 Polymorphism Is Associated with Severe Obesity in North India

ABSTRACT: Background:Obesity is a very common disorder resulting from an imbalance between food intake and energy expenditure, and it has a substantial impact on the development of chronic diseases. The aim of this study was to examine the association of INSIG2 (rs7566605) gene polymorphism with obesity and obesity associated phenotypes in North Indian subjects. Methods:The variants were investigated for association in 642 obese and non-obese individuals. The genotyping of INSIG2 (rs7566605) single nucleotide polymorphism was analyzed by the TaqMan allelic discrimination protocol. Results:A significant association was observed for INSIG2 (rs7566605) single nucleotide polymorphism with obesity and obesity-related phenotypes. Furthermore, a significant relationship was found between the rs7566605 and insulin, homeostasis model of assessment-insulin resistance, the percentage of body fat, fat mass, leptin, and adiponectin. Conclusion:The present study observed significant association between INSIG2 (rs7566605) single nucleotide polymorphism and obesity, as well as obesity-associated phenotypes in North Indian population.

SUBMITTER: Prakash J

PROVIDER: S-EPMC5459941 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Common Genetic Variant of insig2 Gene rs7566605 Polymorphism Is Associated with Severe Obesity in North India

Prakash Jai J Mittal Balraj B Apurva Srivastava S Shally Awasthi A Pranjal Srivastava S Neena Srivastava S

Iranian biomedical journal 20170521 4

<h4>Background</h4>Obesity is a very common disorder resulting from an imbalance between food intake and energy expenditure, and it has a substantial impact on the development of chronic diseases. The aim of this study was to examine the association of INSIG2 (rs7566605) gene polymorphism with obesity and obesity associated phenotypes in North Indian subjects.<h4>Methods</h4>The variants were investigated for association in 642 obese and non-obese individuals. The genotyping of INSIG2 (rs756660 ...[more]

PMID: 28160769

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Project description:In a genome-wide association study performed in the Framingham Offspring Cohort, individuals homozygous for the rs7566605 C allele located upstream of insulin-induced gene 2 (INSIG2) were reported to incur an increased risk of obesity. This finding was later replicated in four out of five populations examined. The goal of the study reported here was to assess the role of the INSIG2 single nucleotide polymorphism (SNP) in susceptibility to obesity in the prospective longitudinal Atherosclerosis Risk in Communities (ARIC) study (n = 14,566) and in three other cohorts: the Coronary Artery Risk Development in Young Adults (CARDIA) study (n = 3,888), the Genetic Epidemiology Network of Arteriopathy (GENOA) study (n = 4,766), and extremely obese and lean individuals ascertained at the University of Ottawa (n = 1,502). The combined study sample is comprised of 24,722 white, African-American, and Mexican-American participants.Differences in mean body mass index (BMI) and other anthropometric measures including weight, waist circumference, and waist-to-hip ratio were assessed by a general linear model in individuals categorized by INSIG2 rs7566605 genotype. Multivariable logistic regression was used to predict the risk of obesity (BMI >or= 30 kg/m2).There was no discernable variation in the frequencies of the three INSIG2 SNP genotypes observed between white, Hispanic, and African-American obese individuals and non-obese study subjects. When the relationship between rs7566605 and BMI considered either as a categorical variable or a continuous variable was examined, no significant association with obesity was found for participants in any of the four study populations or in a combined analysis (p = 0.38) under a recessive genetic model. There was also no association between the INSIG2 polymorphism and the obesity-related quantitative traits except for a reduced waist-to-hip ratio in white ARIC study participants homozygous for the C allele, and an increased waist-to-hip ratio in African-Americans in the ARIC cohort with the same genotype (p = 0.04 and p = 0.01, respectively). An association with waist-to-hip ratio was not seen when the combined study sample was analyzed (p = 0.74).These results suggest that the INSIG2 rs7566605 variant does not play a major role in determining obesity risk in a racially and ethnically diverse sample of 24,722 individuals from four cohorts.

Project description:Single nucleotide polymorphisms associated with lipid metabolism and energy balance are implicated in the weight loss response caused by nutritional interventions. Diet?induced weight loss is also associated with differential global DNA methylation. DNA methylation has been proposed as a predictive biomarker for weight loss response. Personalized biomarkers for successful weight loss may inform clinical decisions when deciding between behavioral and surgical weight loss interventions. The aim of the present study was to investigate the association between global DNA methylation, genetic variants associated with energy balance and lipid metabolism, and weight loss following a non?surgical weight loss regimen. The present study included 105 obese participants that were enrolled in a personalized weight loss program based on their allelic composition of the following five energy balance and lipid metabolism?associated loci: Near insulin?induced gene 2 (INSIG2); melanocortin 4 receptor; adrenoceptor ?2; apolipoprotein A5; and G?protein subunit ?3. The present study investigated the association between a global DNA methylation index (GDMI), the allelic composition of the five energy balance and lipid metabolism?associated loci, and weight loss during a 12 month program, after controlling for age, sex and body mass index (BMI). The results demonstrated a significant association between the GDMI and near INSIG2 locus, after adjusting for BMI and weight loss, and significant trends were observed when stratifying by gender. In conclusion, a combination of genetic and epigenetic biomarkers may be used to design personalized weight loss interventions, enabling adherence and ensuring improved outcomes for obesity treatment programs. Precision weight loss programs designed based on molecular information may enable the creation of personalized interventions for patients, that use genomic biomarkers for treatment design and for treatment adherence monitoring, thus improving response to treatment.

Dataset Information

Common Genetic Variant of insig2 Gene rs7566605 Polymorphism Is Associated with Severe Obesity in North India

Publications

Common Genetic Variant of insig2 Gene rs7566605 Polymorphism Is Associated with Severe Obesity in North India

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