Relationship between endothelial nitric oxide synthase gene polymorphisms and the risk of myocardial infarction in the Algerian population

Introduction: Endothelial nitric oxide synthase (eNOS), the enzyme in charge of nitric oxide production, plays a crucial role in vascular biology. However, the impact of single nucleotide polymorphisms (SNPs) affecting the gene encoding for eNOS (eNOS) on coronary artery diseases remains under debate and no data were available at present in populations originating from Mahghreb.Aim of the Study: Our purpose was to evaluate the association between the eNOS -786T/C and +894G/T SNPs and (i) the risk of myocardial infarction (MI) and (ii) variations in systolic (SBP) and diastolic (DBP) blood pressure values.Patients and Methods: Concerning MI, the SNPs were characterised in a casecontrol study (70 cases vs 68 controls) based on the male population originating from Oran, Algeria.Results: The associations with blood pressure values were assessed in anenlarged control group including 115 male subjects. Since the -786T/CSNP could not be associated to MI, the genotype distribution of the+894G/T genotypes signifi cantly differed between MI cases and controls(p=0.025). The risk of MI (odds ratio) associated to the +894G/T SNP wasestimated to 1.2 (95%CI=[1.03;1.32]). The haplotype analysis confi rmedthis association and the absence of impact of the -786T/C SNP. On the other hand, no consistent association was shown between the two SNPs and SBP or DBP.Conclusion: As observed in other populations, the eNOS +894G/T SNPwas associated with MI in the Algerian population but the mechanismunderlying the effect could not be related to variations in blood pressure.Keywords: Endothelial nitric oxide synthase, myocardial infarction, blood pressure, genetic epidemiology

Analysis of the HLA population data (AHPD) submitted to the 15th International Histocompatibility/Immunogenetics Workshop by using the Gene[rate] computer tools accommodating ambiguous data (AHPD project report)

During the 15th International Histocompatibility and Immunogenetics Workshop (IHIWS), 14 human leukocyte antigen (HLA) laboratories participated in the Analysis of HLA Population Data (AHPD) project where 18 new population samples were analyzed statistically and compared with data available from previous workshops. To that aim, an original methodology was developed and used (i) to estimate frequencies by taking into account ambiguous genotypic data, (ii) to test for Hardy–Weinberg equilibrium (HWE) by using a nested likelihood ratio test involving a parameter accounting for HWE deviations, (iii) to test for selective neutrality by using a resampling algorithm, and (iv) to provide explicit graphical representations including allele frequencies and basic statistics for each series of data. A total of 66 data series (1–7 loci per population) were analyzed with this standard approach. Frequency estimates were compliant with HWE in all but one population of mixed stem cell donors. Neutrality testing confirmed the observation of heterozygote excess at all HLA loci, although a significant deviation was established in only a few cases. Population comparisons showed that HLA genetic patterns were mostly shaped by geographic and/or linguistic differentiations in Africa and Europe, but not in America where both genetic drift in isolated populations and gene flow in admixed populations led to a more complex genetic structure. Overall, a fruitful collaboration between HLA typing laboratories and population geneticists allowed finding useful solutions to the problem of estimating gene frequencies and testing basic population diversity statistics on highly complex HLA data (high numbers of alleles and ambiguities), with promising applications in either anthropological, epidemiological, or transplantation studies

Genetic heterogeneity in Algerian human populations

The demographic history of human populations in North Africa has been characterized by complex processes of admixture and isolation that have modeled its current gene pool. Diverse genetic ancestral components with different origins (autochthonous, European, Middle Eastern, and sub-Saharan) and genetic heterogeneity in the region have been described. In this complex genetic landscape, Algeria, the largest country in Africa, has been poorly covered, with most of the studies using a single Algerian sample. In order to evaluate the genetic heterogeneity of Algeria, Y-chromosome, mtDNA and autosomal genome-wide makers have been analyzed in several Berber- and Arab-speaking groups. Our results show that the genetic heterogeneity found in Algeria is not correlated with geography or linguistics, challenging the idea of Berber groups being genetically isolated and Arab groups open to gene flow. In addition, we have found that external sources of gene flow into North Africa have been carried more often by females than males, while the North African autochthonous component is more frequent in paternally transmitted genome regions. Our results highlight the different demographic history revealed by different markers and urge to be cautious when deriving general conclusions from partial genomic information or from single samples as representatives of the total population of a region.This study was supported by the Ministerio de Economía y Competitividad grant CGL2013-44351-P and by Direcció General de Recerca, Generalitat de Catalunya grant 2014SGR866