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PRDM16 Gene Polymorphism Is Associated with Obesity and Blood Lipids Profiles in Saudi Population.

ABSTRACT: AIMS:The PR domain containing 16 (PRDM16) gene and the Phosphodiesterase 4D (PDE4) gene are both an essential regulators in the thermogenesis process in the brown adipose tissues (BAT). The influence of polymorphisms in those genes on obesity and blood lipids profile is unknown particularly in the Saudi population, so the current study is aiming to explore that. METHODS:A case control format was used that involved 89 obese individual and 84 non-obese (control). The PRDM16 (rs2651899) and PDE4D (rs295978) polymorphisms were genotyped using KASP™ (Competitive Allele-Specific PCR) method. RESULTS:The distributions of the AA, GG, and AG genotypes of PRDM16 (rs2651899) polymorphism were 0.19, 0.26 and 0.54, respectively. While the distribution of the mutated allele A was 0.7 in the obese group comparing to 0.34 in the non-obese group. Participants with the mutated genotypes, AA and AG, of PRDM16 (rs2651899) polymorphism were significantly more likely to be obese as compared to participants with wild type genotype (OR = 21, 95% CI = 5.4190 to 84.4231, p value < 0.0001 and OR = 44.6, 95% CI = 11.5984 to 172.0157, p value < 0.0001, respectively). The wild type GG genotype of this polymorphism was associated with higher blood cholesterol, HDL and LDL but lower blood triglyceride compared with the mutated genotypes (p = 0.003, p = 0.008, p = 0.02 and p = 0.003, respectively). In contrast, PDE4D (rs295978) polymorphism was not associated with risk of obesity and had no effects on blood lipids profile. CONCLUSIONS:We found that the PRDM16 polymorphism (rs2651899) is a risk factor for obesity and influence blood lipids profiles significantly in Saudi population. While the PDE4D (rs295978) polymorphism didn’t show significant effect on risk of obesity or blood lipids profiles.

SUBMITTER: AlAmrani A

PROVIDER: S-EPMC6025268 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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<i>PRDM16</i> Gene Polymorphism Is Associated with Obesity and Blood Lipids Profiles in Saudi Population.

AlAmrani Aishah A AbdelKarim Mouaadh M AlZoghaibi Mohammed M

Journal of clinical medicine 20180608 6

<h4>Aims</h4>The PR domain containing 16 (<i>PRDM16</i>) gene and the Phosphodiesterase 4D (<i>PDE4</i>) gene are both an essential regulators in the thermogenesis process in the brown adipose tissues (BAT). The influence of polymorphisms in those genes on obesity and blood lipids profile is unknown particularly in the Saudi population, so the current study is aiming to explore that.<h4>Methods</h4>A case control format was used that involved 89 obese individual and 84 non-obese (control). The < ...[more]

PMID: 29890628

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Project description: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.

Dataset Information

PRDM16 Gene Polymorphism Is Associated with Obesity and Blood Lipids Profiles in Saudi Population.

Publications

<i>PRDM16</i> Gene Polymorphism Is Associated with Obesity and Blood Lipids Profiles in Saudi Population.

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