Dataset Information

Molecular dynamic (MD) studies on Gln233Arg (rs1137101) polymorphism of leptin receptor gene and associated variations in the anthropometric and metabolic profiles of Saudi women.

ABSTRACT: The Gln233Arg (A>G; rs1137101) polymorphism of the leptin receptor gene (LEPR) has been investigated extensively and is reported to be associated with different metabolic states. In this investigation, we aimed to study the frequency of Gln233Arg genotypes and alleles in a group of Saudi women stratified by their body mass index (BMI), to correlate the LEPR genotypes with variations in anthropometric, lipid and hormonal parameters and to investigate conformational and structural variations in the mutant LEPR using molecular dynamic (MD) investigations. The study group included 122 Saudi women (normal weight = 60; obese = 62) attending the clinics for a routine checkup. Anthropometric data: height, weight, waist and hip circumference were recorded and fasting serum sample was used to estimate glucose, lipids, ghrelin, leptin and insulin. BMI, W/H ratio, and HOMA-IR values were calculated. Whole blood sample was used to extract DNA; exon 6 of the LEPR gene was amplified by PCR and sequencing was conducted on an ABI 3100 Avant Genetic Analyser. Molecular Dynamic Simulation studies were carried out using different softwares. The results showed the presence of all three genotypes of Gln233Arg in Saudi women, but the frequencies were significantly different when compared to reports from some populations. No differences were seen in the genotype and allele frequencies between the normal weight and obese women. Stratification by the genotypes showed significantly higher BMI, waist and hip circumference, leptin, insulin, fasting glucose and HOMA-IR and lower ghrelin levels in obese women carrying the GG genotype. Even in the normal weight group, individuals with GG genotype had higher BMI, waist and hip circumference and significantly lower ghrelin levels. The MD studies showed a significant effect of the Gln/Arg substitution on the conformation, flexibility, root-mean-square fluctuation (RMSF), radius of gyration (Rg) values, solvent-accessible surface area (SASA) and number of inter- and intra-molecular H-bonds. The results suggest that the structural changes brought about by the mutation, influence the signaling pathways by some unknown mechanism, which may be contributing to the abnormalities seen in the individuals carrying the G allele of rs1137101.

SUBMITTER: Daghestani M

PROVIDER: S-EPMC6375553 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Molecular dynamic (MD) studies on Gln233Arg (rs1137101) polymorphism of leptin receptor gene and associated variations in the anthropometric and metabolic profiles of Saudi women.

Daghestani Maha M Purohit Rituraj R Daghestani Mazin M Daghistani Mamoon M Warsy Arjumand A

PloS one 20190214 2

The Gln233Arg (A>G; rs1137101) polymorphism of the leptin receptor gene (LEPR) has been investigated extensively and is reported to be associated with different metabolic states. In this investigation, we aimed to study the frequency of Gln233Arg genotypes and alleles in a group of Saudi women stratified by their body mass index (BMI), to correlate the LEPR genotypes with variations in anthropometric, lipid and hormonal parameters and to investigate conformational and structural variations in th ...[more]

PMID: 30763324

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Project description:BackgroundThe prevalence of metabolic syndrome varies widely by ethnicity and by the criteria used in its definition.ObjectiveTo identify the optimal cutoff values for waist circumference (WC), waist-to-hip ratio (WHR) and body mass index (BMI) for identifying metabolic syndrome among the Saudi population.DesignNationwide household cross-sectional population-based survey.SettingThirteen health sectors in Saudi Arabia.Subjects and methodsWe used data for subjects in the Saudi Abnormal Glucose Metabolism and Diabetes Impact Study (SAUDI-DM), which was conducted from 2007 to 2009. Using International Diabetes Federation (IDF) criteria, metabolic syndrome and its different components were assessed using anthropometric measurements, blood pressure, fasting plasma glucose, triglycerides and HDL cholesterol. Receiver operating characteristic (ROC) curves were generated to assess sensitivity and specificity for different cutoff values of WC, WHR, and BMI. The Youden index was used to calculate the optimal cutoff value for each anthropometric measurement.Main outcome measure(s)Optimal cutoff value for WC, WHR, and BMI for identifying the risk of metabolic syndrome.ResultsThe prevalence of two or more risk factors for metabolic syndrome was observed in 43.42% of the total cohort of 12126 study participants >=18 years of age. The presence of two or more risk factors were significantly higher among men (46.81%) than women (40.53%) (P < .001). The optimal cutoff values for WC, WHR, and BMI were 92 cm, 0.89, and 25 kg/m2 for men and 87 cm, 0.81 and 28 kg/m2 for women for identifying the risk of metabolic syndrome. The prevalence of elevated triglycerides, blood pressure, and fasting plasma glucose significantly increased with age for both genders.ConclusionsThe proposed WC cutoff values were better than WHR and BMI in predicting metabolic syndrome and could be used for screening people at high risk for metabolic syndrome in the Saudi population.LimitationsNo direct measure of body fatness and fat distribution, cross-sectional design.

Project description:BACKGROUND:Polycystic ovary syndrome (PCOS) is considered as one of the most frequently encountered hormonal pathologies in women during their reproductive years. Leptin and ghrelin, peptide hormones with adipostatic and orexigenic effect, respectively, seem to be involved in the metabolic changes that occur in PCOS. The aim of this study was to determine serum ghrelin and leptin levels in obese and lean Saudi women with PCOS and to investigate their relationship to the metabolic profiles in these women. METHODS:This study was conducted as a prospective, observational, cross-sectional, case-control study, at the Department of Obstetrics and Gynecology, Al-Noor Hospital, Makkah, Kingdom of Saudi Arabia. The study population included 252 women [130 women with PCOS (diagnosed according to the Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus, 2003) and 122 normo-ovulatory women as matched controls] attending the outpatient Gynecology Clinic. Demographic details were recorded, blood was extracted following overnight fast and serum was used for the determination of serum ghrelin and leptin levels and other hormonal and biochemical parameters including total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, glucose, and insulin. Insulin resistance and sensitivity were calculated as HOMA-IR and HOMA-S. RESULTS:No significant differences in ghrelin (P = 0.1830) and leptin (P = 0.8329) levels were detected between the PCOS and control groups. However, ghrelin levels were significantly lower; and leptin levels were significantly higher in obese PCOS patients in comparison with lean patients (P = 0.0001 for both). In the PCOS group, there were significant correlations between ghrelin and leptin levels with Body Mass Index (BMI), waist-hip ratio, total cholesterol, triglycerides, HDL, LDL and insulin levels. Multiple regression analysis demonstrated that insulin was the main determinant for ghrelin (R2 = 0.316) and leptin (R2 = 0.352) levels (P = 0.0001 for both). CONCLUSIONS:Although serum ghrelin and leptin levels were found to be normal in women with PCOS; yet, there is a relationship, possibly linked to obesity, hyperinsulinemia and insulin resistance between these levels and metabolic profile of Saudi PCOS.

Dataset Information

Molecular dynamic (MD) studies on Gln233Arg (rs1137101) polymorphism of leptin receptor gene and associated variations in the anthropometric and metabolic profiles of Saudi women.

Publications

Molecular dynamic (MD) studies on Gln233Arg (rs1137101) polymorphism of leptin receptor gene and associated variations in the anthropometric and metabolic profiles of Saudi women.

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