The Role of Apelin gene polymorphism in obesity

Abstract

Obesity is a major health problem that has reached epidemic levels worldwide. It is considered a highly heritable and genetically heterogeneous disorder. Despite the improvement in our understanding of the genetic basis of obesity, the underlying genetic cause of most families with extreme obesity is still unknown. Obesity is a multifactorial problem that emerges as a result ofcombination of many factors including genetic susceptibility. A significant predisposition to insulin resistance (IR) is observed with obesity, which is a hallmark of Type 2 Diabetes mellitus (T2DM).

Apelin, which is a recent adipokine, was shown to be involved broadly in energy metabolism. It has been established to increase glucose uptake in skeletal muscle and adipose tissue,in vivo and in vitro, via several mechanisms. Moreover, it has important roles in energy expenditure, food intake and vascular integrity in adipose tissue, which collectively affects obesity. Also among its roles, it’s known to have strong vasodilator and inotropic effect.

Genetic association studies now are gaining much appreciation, as trying to spot possible association between certain loci on significant genes and several diseases across people from different ethnicity. Therefore, we aimed toinvestigate a possible association between the genetic variant of APLN rs3115757 and obesity phenotypes as body mass index (BMI) and waist circumference (WC) . Also it was examined if that single nucleotide polymorphism (SNP) can influence IR, thus may be a potential candidate playing role in obesity-associated-T2DM. Moreover, it was examined for association with dyslipidemia and hypertension (HTN) in the studied population. In order to fulfil our aim, this study was conducted on 151 subject women divided into the following groups: a) Control non obese non-diabetic group: This group included 39 normoglycemic individuals. They were lean with (BMI<25). b) Obese non-diabetic group: This group comprised 17obese women with (BMI≥30) but without T2DM. c) Obese T2DM group: This group comprised 95 obese women with (BMI≥30) and suffering from T2DM. All subjects were assessed for anthropometric and metabolic parameters related to obesity and T2DM besides estimation of fasting serum insulin (FSI) levels. In addition,genotypingof APLN rs3115757 was performed. Results of the current study can be summarized as follows: 1) Significantly elevated levels of fasting plasma glucose (FPG), fasting serum insulin(FSI), homeostatic model for isulin resistance (HOMA-IR), BMI and WC values and dyslipidemia occurrence as well as significantly lower values of quantitative insulin sensitivity check index (QUICKI) were observed in obese T2DM group in comparison to control non obese non-diabetic groups. 2) Elevated levels of FPG, FSI, HOMA-IR values and dyslipidemia occurrence as well as lower values of QUICKI were observed in obesenon diabetic group in comparison to control non-obesenon-diabetic group. 3) The genotype distribution of APLN rs3115757 SNP followed Hardy-Weinberg equilibrium in control groups (P>0.05). 4) The genotypes and C/G allelic frequencies of APLN rs3115757 in the studied Egyptian population were determined. 5) Women with GG genotype had significantly higher WC and BMI values as compared to those with CC or CG genotypes. 6) Although there were no significant association between APLN rs3115757 and T2DM, women with GG genotype had significantly higher FSI and HOMA-IR values as well as significantly lower QUICKI value than those with CC or CGgenotypes. 7) G allele is the risk allele for obesity and central obesity. 8) The minor GG genotype was overrepresented in hypertensive patients than those with normal blood pressure but the association didn’t reach a statistically significant level. 9) There were no significant associations between rs3115757 genotypes and values of total cholesterol (TC), low density lipoproteincholesterol (LDL-C), triglycerides (TAG), AST or ALT in the study population.