GHRL, LEP, LEPR genes polymorphism and their association with the metabolic syndrome in the Ukrainian population.

Objective. Many conflicting results have been obtained in the study of leptin (LEP) and leptin receptor (LEPR) gene variants that are associated with the obesity and diabetes possibly due to differences in the study populations. The aim of this study was to evaluate changes in the metabolic hormones (leptin, ghrelin, adiponectin, resistin) levels in the blood of obese patients in relation to the GHRL (rs696217), LEP (rs7799039), LEPR (rs1137100, rs1137101, rs1805094) polymorphism in Ukrainian population. Methods. The study involved 53 obesity cases and 48 non-obesity subjects (controls). The GHRL, LEP, and LEPR genes polymorphism (rs696217, rs7799039, rs1137100, rs1137101, rs1805094) was genotyped using a TaqMan real-time polymerase chain reaction method. Blood hormones (leptin, ghrelin, adiponectin, resistin) were determined with commercially available kits using a Multiskan FC analyzer. Results. The study of the effect of genotypes of the GHRL (rs696217), LEP (rs7799039), and LEPR (rs1137100, rs1805094) polymorphisms on the level of metabolic hormones (leptin, ghrelin, adiponectin, resistin) in the blood of obese patients did not show reliably significant results. Thus, the presence of the LEPR genes (rs1137101) polymorphism in the Ukrainian population indicates an increased risk of the metabolic syndrome development regardless of the homozygous or heterozygous genotype (genotypes AA, AG, GG). Conclusions. We established a significant effect of the presence of the A allele and G allele of the LEPR gene polymorphism (rs1137101) on the level of leptin, ghrelin, adiponectin, and resistin in the serum of patients diagnosed with the metabolic syndrome in the Ukrainian population.

Dual Effect of the GHRL Gene Variant in the Molecular Pathogenesis of Obesity.

Obesity is as a global health problem due to its interaction with complex chronic disorders such as cardiovascular disorders, type 2 diabetes mellitus (T2DM) and cancer. Despite the fact that pathogenesis of obesity is not yet clearly understood, it is associated with a combination of psychological, environmental and various genetic factors. Here, employing a case-control design, we aimed to examine the effects of the GHRL c.152C>T (p.Arg51Gln) (rs34911341) and c.214G>T (p.Leu72Met) (rs696217) markers on susceptibility to obesity in a Turkish-Cypriot population, as well as to evaluate whether these markers affect biochemical parameters and show their putative functional consequences. This study involved 211 Turkish-Cypriot subjects (106 obese and 95 non obese). Genotyping for the GHRL gene polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Our results indicate that the GHRL Leu72Met polymorphism was found to be significantly higher in obese patients, with respect to genotypic (p = 0.0012) and allelic (p = 0.0005) frequencies. Strikingly, the rs696217 GT genotype (heterozygous) had significantly lower serum high-density lipoprotein cholesterol (HDL-C) (p = 0.015) than GG (wild type) genotypes. Overall, Leu72Met susceptibility variant may be considered as risk and crucial marker for both obesity and cholesterol metabolism in the community of Turkish-Cypriots. Thus, the dual effect of the GHRL gene Leu72Met variant may be used for clinical diagnosis.

Upregulation of Ghrelin Gene Expression in the Excluded Stomach of Obese Women with Type 2 Diabetes After Roux-en-Y Gastric Bypass in the SURMetaGIT Study.

BACKGROUND: Mechanisms of type 2 diabetes remission (T2Dr) after Roux-en-Y gastric bypass (RYGB) in obese patients appear to involve gastrointestinal hormones. OBJECTIVE: The objective of this study is to explore changes in ghrelin plasma levels and ghrelin gastrointestinal gene expression (GHRL) after RYGB, and their relationships to T2Dr. SETTING: In 20 obese women with T2D, before and 3 months after RYGB, we assessed GHRL expression by microarray and quantitative RT-PCR in gastrointestinal biopsy samples and plasma levels of ghrelin. RESULTS: After RYGB, GHRL expression increased in the excluded stomach (p < 0.05) with no change in other gastrointestinal sites. There were no significant changes in ghrelin plasma levels and no correlations with T2Dr. CONCLUSIONS: After RYGB, over-expression of GHRL gene occurs only in the excluded stomach with no correlation to T2Dr.

Obesity and variants of the GHRL (ghrelin) and BCHE (butyrylcholinesterase) genes.

Ghrelin coded by the GHRL gene is related to weight-gain, its deactivation possibly depending on its hydrolyzation by butyrylcholinesterase (BChE) encoded by the BCHE gene, an enzyme already associated with the body mass index (BMI). The aim was to search for relationships between SNPs of the GHRL and BCHE genes with BChE activity, BMI and obesity in 144 obese and 153 nonobese Euro-Brazilian male blood donors. In the obese individuals, a significant association with higher BChE activity, in the 72LM+72MM; -116GG genotype class (GHRL and BCHE genes, respectively) was noted. No significant differences were found otherwise, through comparisons between obese and control individuals, of genotype and allele frequencies in SNPs of the GHRL gene (Arg51Gln and Leu72Met), or mean BMI between 72LL and 72LM+72MM genotypes. Although there appears to be no direct relationship between the examined GHRL SNPs and BMI, the association of the 72M SNP with higher BChE activity in obese subjects probably points to a regulatory mechanism, thereby implying the influence of the GHRL gene on BChE expression, and a consequential metabolic role in the complex process of fat utilization.

Obesity and variants of the GHRL (ghrelin) and BCHE (butyrylcholinesterase) genes

Ghrelin coded by the GHRL gene is related to weight-gain, its deactivation possibly depending on its hydrolyzation by butyrylcholinesterase (BChE) encoded by the BCHE gene, an enzyme already associated with the body mass index (BMI). The aim was to search for relationships between SNPs of the GHRL and BCHE genes with BChE activity, BMI and obesity in 144 obese and 153 nonobese Euro-Brazilian male blood donors. In the obese individuals, a significant association with higher BChE activity, in the 72LM+72MM; -116GG genotype class (GHRL and BCHE genes, respectively) was noted. No significant differences were found otherwise, through comparisons between obese and control individuals, of genotype and allele frequencies in SNPs of the GHRL gene (Arg51Gln and Leu72Met), or mean BMI between 72LL and 72LM+72MM genotypes. Although there appears to be no direct relationship between the examined GHRL SNPs and BMI, the association of the 72M SNP with higher BChE activity in obese subjects probably points to a regulatory mechanism, thereby implying the influence of the GHRL gene on BChE expression, and a consequential metabolic role in the complex process of fat utilization.