Associations of the PPARα and Lipoprotein Lipase Enzyme Gene Polymorphisms with Dyslipidemia in Obese and Non-obese Males.

Background: Peroxisome proliferator-activated receptor α (PPARα) is a nuclear transcription factor responsible for gene expression, particularly those associated with lipid metabolism. The lipoprotein lipase enzyme (LPL) is considered a key enzyme in lipid metabolism and transport. The link between dyslipidemia and obesity is well understood. Dyslipidemia is also an established risk feature for cardiovascular disease. Thus, it becomes progressively essential to identify the role of genetic factors as risk markers for the development of dyslipidemia among obese males. Methods: A case-control study was performed including 469 males. Anthropometric characteristics and serum lipid profiles such as triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were evaluated. Genomic DNA extraction and purification were performed using whole blood samples. Restriction enzyme fragment length polymorphism was used to genotype PPARα and LPL single nucleotide polymorphisms. The associations between these polymorphisms and dyslipidemia were examined. Results: The CC and CG genotypes of PPARα gene polymorphisms were significantly associated with higher TC and LDL-C levels (P<0.05). The TT genotype of the LPL gene polymorphism was significantly associated with higher TG levels and lower HDL-C levels (P<0.05). In contrast, the GG genotype may have a protective action against dyslipidemia. Conclusion: The study reaches the interesting conclusion that there was a significant association between PPARα as well as LPL gene polymorphisms and dyslipidemia among obese and non-obese males.

Adiponectin gene polymorphisms as a predictor for development of type 2 diabetes mellitus in Iraqi population.

BACKGROUND: Type 2 diabetes mellitus (T2DM) incidence is increasing globally and nationally. The etiology of the disease includes environmental and genetic factors. Polymorphism of adiponectin gene was found to be implicated in the pathogenesis of T2DM in numerous populations. METHODS: A case-control study was conducted to assess the association of rs2241766 and rs822395 SNPs of adiponectin gene (ADIPOQ) with T2DM in Iraqi population. The study included 400 patients with T2DM and 400 healthy individuals served as a control group. Serum lipid concentrations, insulin level and the index of insulin resistance (HOMA) were measured. The genotyping of ADIPOQ for rs2241766 and rs822395 SNPs was performed by PCR-RFLP. RESULTS: The genotype distribution of rs2241766 SNP indicated a significant increase of carriers of the homozygous GG (OR: 5.04, CI95%: 2.27-11.19, P: 0.0001) and heterozygous TG (OR: 1.7, CI95%: 1.22-2.39, P: 0.002) variants when compared with those of the wild type, suggesting a risk factor of 2 and 5 to develop the disease. The minor allele frequency (MAF) G was observed to be significantly (P: 0.0001) higher in patients (22%) when compared with the control group (11.74%). Results of rs822395 SNP failed to exhibit a significant difference. Changes of BMI, cholesterol, triglycerides, insulin and insulin resistance index values in the diabetic patients seemed to be parallel with the presence of MAF of rs2241766 SNP. CONCLUSION: The rs2241766T>G SNP of adiponectin gene is a risk factor for the development of T2DM in Iraqi population and directs the changes of serum lipid concentrations as well as insulin resistance.

FTO gene polymorphisms (rs9939609 and rs17817449) as predictors of Type 2 Diabetes Mellitus in obese Iraqi population.

BACKGROUND: The variation of the SNPs in FTO (fat mass and obesity associated) gene are improved to be associated with obesity and type 2 diabetes (T2DM) in some ethnic groups for example in European while, this consistency is controversial in Asians and there were few studies in Iraqi population about the effect of this gene on the development of T2DM in obese patients. Therefore, the objective of this study is to investigate the impact of the two common FTO gene variants in the development of T2DM in obese Iraqi patients. METHODS: A case-control study in which the FTO gene variants rs9939609 and rs17817449 were genotyping in a total of 800 individuals, 400 T2DM obese patients (patients group) and 400 healthy control obese volunteers (control group) to explore the relation of these SNPs with T2DM in obese Iraqi population. The patients group was enrolled from diabetic clinic in Al Najaf al Ashraf based on WHO guidelines of T2DM. From whole blood the DNA was extraction and genotyped by using ScaI and AlwNI enzymes respectively in the PCR-RFLP technique. Multinomial logistic regression was applied to compare the proportions of genotypes and alleles. The odd's ratio, t-test P value at 95% confidence interval were measured before and after adjustment of BMI, age and sex adjustment. The genetic power, Hardy Weinberg equilibrium and haplotype analysis were tested in the present study. RESULTS: It was observed that the presence of T allele in the two SNPs rs9939609 and rs17817449 in the FTO gene polymorphisms was associated with increased risk for the development of T2DM in Iraqi obese individuals. The minor allele (T) in rs9939609 was significantly higher (P=0.0001) in T2DM (31.25%) when compared with that of the control obese group (20%). The Homozygous genotype (TT) significantly (OR=3.25, CI 95% 1.87-5.64, P=0.000) increased the risk of T2DM by three folds with respect to those of wild type (AA) after adjustment for age, sex and BMI, furthermore, it was significantly increased the risk in the dominant, recessive and additive models (P=0.000,0.000 and 0.0001 respectively). The T allele in rs17817449 was also significantly higher (P=0.0001) in patients group (36.25%) when compared with that of the control group (27.25%). The Heterozygous genotype (TG) significantly (OR=2.24, CI 95% 1.65-3.04, P=0.000) increased the risk of T2DM more than two folds with respect to those of wild type (GG) after adjustment for age, sex and BMI, and it was significantly increased the risk in the dominant models (P=0.000). In the relation to the phenotypic parameters the two SNPs were significantly associated with increased BMI, LDL, insulin and HOMA-IR and a decrease the HDL levels. CONCLUSION: The FTO gene polymorphisms rs9939609 and rs17817449 play a role in the in the development of insulin resistance and hence occurrence of type 2 DM in obese patients.