Analysis of vascular endothelial growth factor (VEGF) insertion/deletion gene polymorphism and environmental risk factors in sample of Algerian population with neovascular age-related macular degeneration (nAMD) / Analyse du polymorphisme insertion/délétion du gène de facteur de croissance endothélial vasculaire (VEGF) et des facteurs de risque environnementaux dans un échantillon de la population algérienne atteinte de la dégénérescence maculaire liée à l'âge néovasculaire (DMLAn)

Background: Increasing evidence shows that genetic and environmental factors can influence neovascular age-related macular degeneration (nAMD) risk. The aim of this study was first to analyse the association of insertion/deletion polymorphism in VEGF gene and environmental factors with the risk of nAMD, and then to investigate whether these factors have an impact on the age of onset of nAMD in a sample of the Algerian population. Methods: Seventy two patients with nAMD and one hundred twenty-four controls were recruited; standardized questionnaire was used to collect information regarding underlying systemic diseases and important environmental factors. Genotyping of VEGF (I/D) SNP was conducted using PCR-based assay approach, and statistical analyses were conducted using IBM SPSS statistics 21. Results: A significant association was reported of age (p < 0.05), smoking (p = 0.02), alcohol (p < 0.01), hypertension (p = 0.04), hyperlipidaemia (p = 0.008) and thyroid disease (p = 0.03) with nAMD. Also, Thyroid disease may have a role in accelerating the development of nAMD in an earlier age in our sample (p < 0.001). No association was found between the VEGF ­ 2549 I/D genotype and the presence of nAMD (p = 0.27), neither with the age of onset of nAMD (p = 0.21). Conclusion: Our results suggest that age, smoking, alcohol, hypertension, hyperlipidaemia and thyroid diseases are possible risk factors that could increase the risk of nAMD in a sample of Algerian population. In addition, VEGF ­ 2549 I/D might not be associated with the risk of nAMD development. Finally, thyroid disease may accelerate the development of nAMD in an earlier age.

Introduction: Un nombre croissant de preuves montrent que les facteurs génétiques et environnementaux peuvent influencer le risque de la forme néovasculaire de la dégénérescence maculaire liée à l'âge (DMLAn). L'objectif de cette étude était d'abord d'analyser l'association du polymorphisme d'insertion/délétion dans le gène VEGF et des facteurs environnementaux avec le risque de la DMLAn, puis d'étudier si ces facteurs ont un impact sur l'âge d'apparition de cette maladie dans un échantillon de population algérienne. Méthodes: Soixante-douze patients atteints de la DMLA et 124 témoins ont été recrutés ; un questionnaire standardisé a été utilisé pour recueillir des informations concernant les maladies systémiques sous-jacentes et les facteurs environnementaux importants. Le génotypage du SNP VEGF (I/D) a été réalisé par une l'approche de PCR standard, et les analyses statistiques ont été réalisées à l'aide du logiciel IBM SPSS statistics 21. Résultats: Une association significative a été rapportée entre l'âge (p < 0,05), le tabagisme (p = 0,02), l'alcool (p < 0,01), l'hypertension (p = 0,04), l'hyperlipidémie (p = 0,008) et les maladies thyroïdiennes (p = 0,03) avec la DMLAn. Les maladies thyroïdiennes peuvent jouer un rôle dans l'accélération du développement de la DMLAn à un âge plus précoce dans notre échantillon (p < 0,001). Aucune association n'a été trouvée entre le génotype VEGF ­ 2549 I/D et la présence de la DMLA néovasculaire (p = 0,27), ni avec l'âge d'apparition de cette pathologie (p = 0,21). Conclusion: Nos résultats suggèrent que l'âge, le tabagisme, l'alcool, l'hypertension, l'hyperlipidémie et les maladies thyroïdiennes sont des facteurs de risque possibles qui pourraient augmenter le risque de la DMLA néovasculaire. De plus, le VEGF ­ 2549 I/D pourrait ne pas être associé au risque de développement de la DMLA. Enfin, les maladies thyroïdiennes pourraient accélérer le développement de la DMLAn à un âge plus précoce.

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.

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.

A study on the polymorphisms of the renin-angiotensin system pathway genes for their effect on blood pressure levels in males from Algeria.

INTRODUCTION: Several studies have assessed the relationship between blood pressure (BP) and polymorphisms within the genes encoding angiotensinogen (AGT), angiotensin II type 1 receptor (AT1R) and angiotensin-converting enzyme (ACE). However, considering the relatively large discrepancy in frequency and impact of these variants between ethnic groups and populations, still unavailable data from Algerian population are needed. OBJECTIVE: Our purpose is to evaluate the association between the AGT M235T, AT1R +1166A/C and ACE I/D polymorphisms and variations in systolic (SBP), diastolic (DBP) and pulse pressure (PP) values. METHODS: The associations with BP were assessed in a representative sample of 115 male subjects free of coronary heart disease (CHD). The AGT M235T, AT1R +1166A/C and ACE I/D polymorphisms were determined by PCR-ASO and PCR-RFLP analysis, respectively. RESULTS: We showed no associations between the AGT M235T, AT1R +1166A/C nor the ACE I/D polymorphisms with variations in BP values. However, concerning the ACE I/D polymorphism, subjects carrying the ACE I allele tended to have higher SBP (+4.1 mmHg) and PP values (+3.2 mmHg) than DD subjects (adjusted p = 0.087 and p = 0.102, respectively). CONCLUSION: The ACE I/D polymorphism needs further investigation in a larger Algerian study, especially concerning its putative impact on SBP and PP.

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.

Association of ornithine transcarbamylase gene polymorphisms with hypertension and coronary artery vasomotion.

BACKGROUND: Previous studies have suggested that the activity of enzymes involved in the urea cycle may modulate nitric oxide (NO) production, arterial vasomotion, and hypertension. Our aim was to determine whether hypertension and coronary vasomotion could be associated with polymorphisms within the ornithine transcarbamylase (OTC) gene, located on chromosome X and coding for a key-enzyme of the urea cycle. METHODS: Among 11 OTC polymorphisms that were originally selected from databases, the tag single-nucleotide polymorphism (SNP) rs5963409 and the independent SNP rs1800321 were tested for association with hypertension in two independent population samples recruited in Northern (Multinational MONItoring of trends and determinants in CArdiovascular disease (MONICA) study, n = 1,138) and Western (Etude du Vieillissement Artériel (EVA) study, n = 1,166) France. The vasomotor response of coronary arteries to methylergonovine maleate and isosorbide dinitrate was also evaluated in an independent sample (the vasomotion study, n = 121). RESULTS: In males, the frequency of the rs5963409 minor allele was consistently higher in hypertensive (HT) than in normotensive subjects in the MONICA and EVA studies. In the combined sample, the rs5963409 minor allele was associated with an increased risk of hypertension (odds ratio (OR) (95% confidence interval (CI)) = 1.45 (1.10-1.90); P = 0.008). This association was independent of classical confounding factors. Consistently, rs5963409 minor allele was associated with a greater susceptibility to vasoconstriction in response to methylergonovine maleate (P = 0.0072). In contrast, no significant association between rs5963409 and hypertension could be detected in females. CONCLUSION: Our results suggest that the OTC rs5963409 polymorphism may be associated with hypertension and coronary vasomotion in males.

Characterization of arginase 1 gene polymorphisms in the Algerian population and association with blood pressure.

OBJECTIVES: (i) To characterize the polymorphism of arginase 1 (ARG1), a new candidate gene in coronary heart disease (CHD), in the Algerian population; (ii) To evaluate the effect of common ARG1 single nucleotide polymorphisms (SNPs) on blood pressure (BP) values; and (iii) To compare the data with those previously obtained in French populations. METHODS: Eleven ARG1 SNPs selected from databases were characterized in a representative sample of 117 Algerian and 92 French males free of CHD. Relevant SNPs for association studies with BP were selected on the basis of their allele frequencies and pairwise linkage disequilibrium. RESULTS: ARG1 allele frequencies and haplotype distribution significantly differed between Algerian and French subjects. The rs2781667C/T polymorphism was associated with decreased systolic BP in Algerian subjects. This association contrasted with previous data we reported in the French population. The discrepancy would be explained by the difference in haplotype distribution between Algerian and French subjects. CONCLUSION: These data support the role of ARG1 in vascular pathophysiology, but the functional mutations remain to be identified.