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.

Factors associated with non-adherence to insulin in Type 1 and Type 2 diabetes mellitus patients in Western region of Algeria, Tlemcen: a cross-sectional study.

Introduction: adherence to drugs is critical for achieving the best clinical results in the treatment of chronic diseases. Adherence to chronic drugs might be influenced by beliefs about medications and other variables. The goal of this study was to assess relevant determinants of medication adherence in Algerian population with insulin-dependent diabetes. Methods: from July 1st 2019 to February 29th 2020, a cross-sectional study was conducted. Participants who had been on insulin for at least 6 months were recruited from Tlemcen (Algeria) clinics in secondary care settings. Patients were invited to a face-to-face interview, in order to complete out the Morisky Medication Adherence Scale-8 (MMAS) tools to report their attitudes towards medication adherence and views about their insulin. The recruited patients' socio-demographic data was also collected. The related determinants of chronic drug non-adherence in the tested population were identified using a stepwise binary logistical regression model. Results: in this study, 147 patients out of 400 were not adhering to their insulin therapy (36.5%). Insulin non-adherence was linked to single status (AOR=2.088, CI=1.180-3.694), non-insurance (AOR=2.949, CI=1.323-6.572), number of daily insulin injections (AOR=1.269, CI=1.033-1.559), unawareness of the insulin regimen (AOR=3.528, CI=1.453-8.565), hypertension (AOR= 3.497, CI=1.98-6.154) and the non-practice of self-monitoring of blood glucose (SMBG) (AOR=2.635, CI=1.472-4.718). Conclusion: insulin adherence in Algerians is still well below international standards. This study improved the understanding of the factors affecting the non-adherence to insulin among diabetics and may be used as a baseline to target; throughout educational programs; the sub-populations identified as non-adherents.

Molecular mimicry between varicella, measles virus and Hsp60 in type 1 diabetes associated HLA-DR3/DR4 molecules.

BACKGROUND AND AIMS: Type 1 diabetes (T1D) is a multifactorial autoimmune disease that combines genetics and environmental factors. The aim of this study is to determine the environmental risk factors and to investigate how virals infections are risks factors for type 1 diabetics whom have HLA DR3/DR4 predisposition in our population. METHODS: This study includes 233 subjects, 145 diabetics and 88 controls from regions of the extreme western of Algeria. All the informations related to the disease were collected using predesigned questionnaire. Using in silico approach, we attempt to improve the understanding of this analytical result by molecular mimicry, which is associated with the breakdown of several autoimmune pathologies. RESULTS: The statistical study showed that history of varicella and measles infection and T1D related inheritance and type 2 diabetes are risk factors for T1D in the population of Tlemcen. We have determined the homologous antigenic regions between the glycoprotein "gE" of the varicella virus, the "hemagglutinin" of measles and the human protein "HSP60" at the level of their sequence and 3D structure. These cross-reactive epitopes bind to MHC class II molecules (HLA DR3/DR4) that predispose to T1D but not to MHC class II molecules (HLA DR2) that protect against T1D. This epitopes induce Th2 cells but only "hemagglutinin" and "Hsp60" can activate Th1 differentiation. This indicates their potential to destroy pancreatic cells ß. CONCLUSION: Our study can allow us to adapt biological markers to genetically predisposed T1D and to establish a preventive strategy for healthy genetic predisposed individuals in Tlemcen population.

Lack of association between genetic variants in the 19q13.32 region and CHD risk in the Algerian population: a population-based nested case-control study.

BACKGROUND: Coronary Heart Disease (CHD) is a major cause of morbidity and mortality over the world; intermediate traits associated with CHD commonly studied can be influenced by a combination of genetic and environmental factors. OBJECTIVE: We found previously significant association between three genetic polymorphisms, and the lipid profile variations in the Algerian population. Considering these findings, we therefore decided to assess the relationships between these polymorphisms and CHD risk. METHODS: We performed a population-based, cross-sectional study, of 787 individuals recruited in the city of Oran, in which, a nested case-control study for MetS, T2D, HBP, obesity and CHD were performed. Subjects were genotyped for four SNP rs7412, rs429358 rs4420638 and rs439401 located in the 19q13.32 region. RESULTS: The T allele of rs439401 confers a high risk of hypertension with an odds ratio (OR) of 1.46 (95% CI [1.12-1.9], p = 0.006) and the G allele of rs4420638 was significantly associated with a decreased risk of obesity, OR 0.48 (95% CI [0.29-0.81], p = 0.004). No associations were found for MetS, T2D and CHD. CONCLUSION: Although the studied genetic variants were not associated with the risk of CHD, the 19q13.32 locus was associated with some of the cardiometabolic disorders in Algerian subjects.

Genetic Determinants of Dyslipidemia in African-Based Populations: A Systematic Review.

Identification of genetic/genomic factors contributing to dyslipidemia is of great interest to prevention and reduction of the onset and burden of cardiovascular diseases in Africa. This systematic review summarizes available data on genetic variants associated with dyslipidemia in populations within Africa. A PubMed and EMBASE database search was conducted to identify all studies published until June 2018 on genetic susceptibility to dyslipidemia in African-based populations, excluding familial hypercholesterolemia. All studies on genetic predispositions of dyslipidemia and respecting the preestablished inclusion criteria were included in this systematic review. Because of high heterogeneity, the data were summarized narratively. Twenty-two studies investigated mostly the targeted genetic variants. A total of 51 polymorphisms in 28 susceptibility genes to dyslipidemia have been associated with a particular trait in the African populations, and through variable effects. Most polymorphisms investigated in Northern Africa seemed to have consistent effects on increasing the level of low-density lipoprotein cholesterol (LDL-C), total cholesterol, and triglycerides in patients with diabetes, myocardial infarction, coronary artery disease, and metabolic syndrome. By contrast, only Ser447Ter and C49620T variants were associated with increased LDL-C in sub-Saharan Africa. Despite few studies available in this context in the literature, certain genetic variants were consistently associated with dyslipidemia especially in Northern Africa as highlighted in this analysis. Further data, particularly from genome-wide association studies, would help establish an African-specific reference for genetic susceptibility markers of dyslipidemia.

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.

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.