Associations of common SNPs in the SORT1, GCKR, LPL, APOA1, CETP, LDLR, APOE genes with lipid trait levels in an Algerian population sample.

Genome-wide association studies have identified many lipid-associated loci primarily in European and Asian populations. In view of the differences between ethnic groups in terms of the frequency and impact of these variants, our objective was to evaluate the relationships between eight lipid-associated variants (considered individually and in combination) and fasting serum triglyceride, total cholesterol, HDL- and LDL-cholesterol levels in an Algerian population sample (ISOR study, n = 751). Three SNPs (in SORT1, CETP and GCKR) were individually associated with lipid level variations. Moreover, the risk allele scores for total cholesterol, triglyceride and LDL-C levels (encompassing between three and six SNPs) were associated with their corresponding lipid traits. Our study is the first to show that some of the lipid-associated loci in European populations are associated with lipid traits in Algerians. Although our results will have to be confirmed in other North African populations, this study contributes to a better understanding of genetic susceptibility to lipid traits in Algeria.

Examination of the brain natriuretic peptide rs198389 single-nucleotide polymorphism on type 2 diabetes mellitus and related phenotypes in an Algerian population.

BACKGROUND: In European populations, the NPPB rs198389 single nucleotide polymorphism (SNP) is associated with a reduced risk of type 2 diabetes mellitus (T2DM). We investigated the putative associations between NPPB rs198389, the T2DM risk and quantitative metabolic traits in an Algerian population. METHODS: The association analysis was performed as a T2DM case-control study (with 78 cases and 645 controls) nested into the ISOR population-based study. RESULTS: The NPPB rs198389 SNP was not associated with T2DM (odds ratio (OR) [95% confidence interval (CI)]=0.73 [0.51-1.04], p=0.08). However, the C allele was associated with lower fasting plasma insulin levels (p=0.05) and a lower homeostatic model assessment insulin resistance index (p=0.05) in non-diabetic individuals. CONCLUSION: The NPPB rs198389 SNP might modulate fasting insulin levels in an Algerian population.

The TCF7L2 rs7903146 polymorphism, dietary intakes and type 2 diabetes risk in an Algerian population.

BACKGROUND: The transcription factor 7-like 2 (TCF7L2) gene is the most significant genetic risk factor for type 2 diabetes (T2D). Association analyses were performed on participants (n = 751, aged between 30 and 64) in the ISOR population-based study in the city of Oran. Dietary intakes were estimated using a weekly food frequency questionnaire. RESULTS: The T allele of the rs7903146 single nucleotide polymorphism (SNP) was associated with lower body weight (p = 0.02), lower BMI (p = 0.009), lower waist circumference (p = 0.01) and a lower waist-to-hip ratio (p = 0.02). The T allele was associated with a significantly higher risk of T2D (odds ratio (OR) (95% confidence interval) = 1.55 (1.09-2.20), p = 0.01) and this association was independent of BMI. When considering the T2D risk, there were nominal interactions between the rs7903146 SNP and dessert (p = 0.05) and milk intakes (p = 0.01). The T2D risk was greater in T allele carriers with high dessert and milk intakes (OR = 2.61 (1.51-4.52), p = 0.0006, and 2.46 (1.47-4.12), p = 0.0006, respectively). In subjects with a high dessert intake, the T allele was also associated with higher fasting plasma glucose concentrations (4.89 ± 0.46 mmol/L in TT subjects, 4.72 ± 0.48 mmol/L in CT subjects and 4.78 ± 0.51 mmol/L in CC subjects; p = 0.03). CONCLUSIONS: The T allele of the rs7903146 SNP is associated with a significantly higher risk of T2D in an Algerian population. This association was further strengthened by a high dessert intake, suggesting that gene-diet interactions increase the T2D risk.

Combined effect of established BMI loci on obesity-related traits in an Algerian population sample.

BACKGROUND: Genome-wide association studies have identified variants associated with BMI in populations of European descent. We sought to establish whether genetic variants that are robustly associated with BMI could modulate anthropometric traits and the obesity risk in an Algerian population sample, the ISOR study. RESULTS: We found that each additional risk allele in the GPS was associated with an increment in the mean [95% CI] for BMI of 0.15 [0.06 - 0.24] kg/m2 (p = 0.001). Although the GPS was also associated with higher waist (p = 0.02) and hip (p = 0.02) circumferences, these associations were in fact driven by BMI. The GPS was also associated with an 11% higher risk of obesity (OR [95%CI] = 1.11 [1.05 - 1.18], p = 0.0004). CONCLUSIONS: Our data showed that a GPS comprising 29 BMI established loci developed from Europeans seems to be a valid score in a North African population. Our findings contribute to a better understanding of the genetic susceptibility to obesity in Algeria.

Impact of APOE gene polymorphisms on the lipid profile in an Algerian population.

BACKGROUND: The importance of apolipoprotein E (APOE) in lipid and lipoprotein metabolism is well established. However, the impact of APOE polymorphisms has never been investigated in an Algerian population. This study assessed, for the fist time, the relationships between three APOE polymorphisms (epsilon, rs439401, rs4420638) and plasma lipid concentrations in a general population sample from Algeria. METHODS: The association analysis was performed in the ISOR study, a representative sample of the population living in Oran (787 subjects aged between 30 and 64). Polymorphisms were considered both individually and as haplotypes. RESULTS: In the ISOR sample, APOE ε4 allele carriers had higher plasma triglyceride (p=0.0002), total cholesterol (p=0.009) and LDL-cholesterol (p=0.003) levels than ε3 allele carriers. No significant associations were detected for the rs4420638 and rs439401 SNPs. Linkage disequilibrium and haplotype analyses confirmed the respectively deleterious and protective impacts of the ε4 and ε2 alleles on LDL-cholesterol levels and showed that the G allele of the rs4420638 polymorphism may exert a protective effect on LDL-cholesterol levels in subjects bearing the APOE epsilon 4 allele. CONCLUSION: Our results showed that (i) the APOE epsilon polymorphism has the expected impact on the plasma lipid profile and (ii) the rs4420638 G allele may counterbalance the deleterious effect of the ε4 allele on LDL-cholesterol levels in an Algerian population.