Genetic diversity of CYP3A4 and CYP3A5 polymorphisms in North African populations from Morocco and Tunisia.

The genes CYP3A4 and CYP3A5 form part of a cluster of cytochrome P450 genes involved in drug metabolism reactions. The allelic variants of these genes CYP3A4*1B, CYP3A4*3, CYP3A4*17 and CYP3A5*3 have been linked both to the reduced catalytic activity of cytochromes and to prostate cancer risk in whites, though scarce data exist for North African populations. The main objective of this study was to describe CYP3A4*3, CYP3A4*17, CYP3A4*1B and CYP3A5*3 allele frequencies and haplotype variation in Moroccan Berbers and the general Tunisian population. The data obtained for the Tunisian participants were consistent with the European allele frequency ranges described, while Moroccan Berbers showed high frequencies of CYP3A4*17 (1.8%), CYP3A4*3 (8.5%) and the CYP3A4*1B/CYP3A5*3 haplotype (18.4%). This haplotype, linked to an increased risk of prostate cancer, was detected at a much higher frequency compared with the present Tunisian population (8.4%) or with reported frequencies for populations such as whites (0.6%) or African Americans (5.3%).

Ethnic composition and genetic differentiation of the Libyan population: insights on Alu polymorphisms.

BACKGROUND: It is thought that the ancient population of Libya was mainly composed of Saharan Berbers. Socio-geographic conditions and historical events have exerted some changes on the composition of the present-day Libyan population. AIM: To screen a set of autosomal Alu markers in a representative sample of the general Libyan population in order to study its ethnic and genetic structure and to re-examine its genetic relationships with Mediterranean and Middle Eastern groups. SUBJECTS AND METHODS: A sample of 190 Libyans was analysed for 17 Alu insertions. The sample was divided according to the Arabic or Berber origin of individuals' surnames. RESULTS: The current general Libyan population is homogeneous and shows considerable genetic diversity compared with other North Mediterranean and North African populations. It shows intermediate genetic distances between Moroccans, Algerians and Tunisians on one side and Egyptian Siwa Berbers on the other. No particular affinities with Middle Eastern groups were detected. CONCLUSION: Alu insertions are useful markers to contribute to the reconstruction of human population history at a microgeographic scale, in particular when the analyses include anthropologically well sampled populations. The present results provide new information to improve understanding some aspects of the complex peopling of North Africa.

Geographical and social influences on genetic diversity within the Egyptian population: analyses of Alu insertion polymorphisms.

BACKGROUND: The geographical location of Egypt at the crossroads of several major cultural areas between North Africa and the Middle East has contributed to its population history. AIM: To analyse the genetic structure of the population living in two geographical parts of Egypt. SUBJECTS AND METHODS: A sample of 112 Egyptians from the North African part of Egypt (Ismailia sample) and a sample of 52 Egyptians from the Asian part Sinai, have been analysed using 10 Alu insertion polymorphisms. RESULTS: The results of the present study showed a significant genetic difference between the Sinai and Ismailia samples. The latter showed an evident genetic affinity with North African populations; whereas the Sinai sample was found to be genetically closer to the Middle East populations. The Sinai sample showed a low average heterozygosity, unlike that found in the Ismailia sample. CONCLUSION: This study provides new insights into the genetic structure of the Egyptian population living in a land bridge between Africa and Asia. Results suggest a genetic discontinuity between the Sinai population and that of the North African part of Egypt. This discontinuity would have been maintained thanks to geo-climatic and social factors.

Genetic position of Bahrain natives among wider Middle East populations according to Alu insertion polymorphisms.

BACKGROUND: The genetic differentiation of Bahrain natives is unclear because of the absence of adequate genetic studies. AIM: Eight Alu insertion polymorphisms have been analysed in Bahrainis and southern Iranians to examine the origins of Bahrainis and to determine their genetic position among wider Middle East populations. SUBJECTS AND METHODS: Two representative samples of 97 Bahrainis and 65 southern Iranians have been determined. Genetic relationships among populations have been estimated by a principal component plot based on the R-matrix software. Mantel tests have been used to check the statistical significance of correlation between genetic and geographic distances. RESULTS: The results show that Bahrainis are in an intermediate genetic position between Emirians and Southern Iranians. Although a general significant correlation between genetic and geographic distances was found between the 16 populations included in the analysis, a lack of this correlation may occur in some particular situations such as the case of populations from southern Iran, United Arab Emirates (UAE) and Bahrain, separated by the Persian Gulf. CONCLUSION: The results support the idea that Bahrainis ancestors were mainly emigrants from Arabia and Iran. In addition the results show that the Iranian component may reach 69.2% of the current genetic pool of Bahrainis.

Genetic differentiation and origin of the Jordanian population: an analysis of Alu insertion polymorphisms.

AIM: Although much of Jordan is covered by desert, its north-western region forms part of the Fertile Crescent region that had given a rich past to Jordanians. This past, scarcely described by historians, is not yet clarified by sufficient genetic data. Thus in this paper we aim to determine the genetic differentiation of the Jordanian population and to discuss its origin. METHODS: A total of 150 unrelated healthy Jordanians were investigated for ten Alu insertion polymorphisms. Genetic relationships among populations were estimated by a principal component (PC) plot based on the analyses of the R-matrix software. RESULTS: Statistical analysis showed that the Jordanian population is not significantly different from the United Arab Emirates population or the North Africans. This observation, well represented in PC plot, suggests a common origin of these populations belonging respectively to ancient Mesopotamia, Arabia, and North Africa. CONCLUSION: Our results are compatible with ancient peoples' movements from Arabia to ancient Mesopotamia and North Africa as proposed by historians and supported by previous genetic results. The original genetic profile of the Jordanian population, very likely Arabian Semitic, has not been subject to significant change despite the succession of several civilizations.

Research of the origin of a particular Tunisian group using a physical marker and Alu insertion polymorphisms.

The aim of this study was to show how, in some particular circumstances, a physical marker can be used along with molecular markers in the research of an ancient people movement. A set of five Alu insertions was analysed in 42 subjects from a particular Tunisian group (El Hamma) that has, unlike most of the Tunisian population, a very dark skin, similar to that of sub-Saharans, and in 114 Tunisian subjects (Gabes sample) from the same governorate, but outside the group. Our results showed that the El Hamma group is genetically midway between sub-Saharan populations and North Africans, whereas the Gabes sample is clustered among North Africans. In addition, The A25 Alu insertion, considered characteristic to sub-Saharan Africans, was present in the El Hamma group at a relatively high frequency. This frequency was similar to that found in sub-Saharans from Nigeria, but significantly different from those found in the Gabes sample and in other North African populations. Our molecular results, consistent with the skin color status, suggest a sub-Saharan origin of this particular Tunisian group.

Research of the origin of a particular Tunisian group using a physical marker and Alu insertion polymorphisms

The aim of this study was to show how, in some particular circumstances, a physical marker can be used along with molecular markers in the research of an ancient people movement. A set of five Alu insertions was analysed in 42 subjects from a particular Tunisian group (El Hamma) that has, unlike most of the Tunisian population, a very dark skin, similar to that of sub-Saharans, and in 114 Tunisian subjects (Gabes sample) from the same governorate, but outside the group. Our results showed that the El Hamma group is genetically midway between sub-Saharan populations and North Africans, whereas the Gabes sample is clustered among North Africans. In addition, The A25 Alu insertion, considered characteristic to sub-Saharan Africans, was present in the El Hamma group at a relatively high frequency. This frequency was similar to that found in sub-Saharans from Nigeria, but significantly different from those found in the Gabes sample and in other North African populations. Our molecular results, consistent with the skin color status, suggest a sub-Saharan origin of this particular Tunisian group.

Mixed origin of the current Tunisian population from the analysis of Alu and Alu/STR compound systems.

During successive historical periods, Tunisia has been a crossroads of multiple civilizations and their corresponding key population movements. The aim of this study was to provide genetic information relating to the mixed origin of the Tunisian population, and to analyze its genetic relationship with other North African and Mediterranean populations. A set of 16 Alu and 3 Alu/STR compound systems has been analyzed in 268 autochthonous Tunisians from the north-center and the south of the country. Our two sampled populations showed no significant differentiation from one another in any of the three Alu/STR compound systems, whereas the analysis of the 16 Alu markers revealed a significant genetic differentiation between them. A sub-Saharan component shown by the three Alu/STR combinations is more noticeable in our north-center sample than in that of the south. The presence of two Alu/STR combinations specific to North African ancestral populations also suggests that the ancient Berber component is relatively more substantial in the north and center regions than in the south. Our Tunisian samples cluster together with other Berber samples from Morocco and Algeria, underpinning the genetic similarity among North Africans regardless of their current linguistic status (Berber or Arabic).

Polymorphism FXII 46C>T and cardiovascular risk: additional data from Spanish and Tunisian patients.

BACKGROUND: Previous studies showed an association between Coagulation Factor XII 46C>T polymorphism and variation in FXII plasma levels, as 46C>T seems to affect the translation efficiency. Case-control studies in Spanish samples indicated that genotype T/T is an independent risk factor for venous thrombosis, ischemic stroke and acute coronary artery disease. In this study, we tried to reaffirm the importance of 46C>T in two samples from Spain and Tunisia. FINDINGS: A Transmission Disequilibrium Test (TDT) based on 101 family trios from Barcelona with one offspring affected by ischemic heart disease and a classical case-control study based on 76 patients with IHD and 118 healthy individuals from North and Centre-South Tunisia were conducted. Subjects were genotyped for 46C>T and data were analyzed accordingly, revealing no association in any of the two samples (TDT: P = 0.16, relative risk 1.17; case-control study: P = 0.59, odds ratio 1.36). CONCLUSION: The results suggest that 46C>T is not a risk factor for ischemic heart disease in any of the two analyzed samples and therefore the polymorphism seems not to be a universal risk factor for cardiovascular diseases.

Apolipoprotein gene polymorphisms and plasma levels in healthy Tunisians and patients with coronary artery disease.

AIM: To analyze apolipoprotein gene polymorphisms in the Tunisian population and to check the relation of these polymorphisms and homocysteine, lipid and apolipoprotein levels to the coronary artery disease (CAD). METHODS: In healthy blood donors and in patients with CAD complicated by myocardial infarction (MI) four apolipoprotein gene polymorphisms [APO (a) PNR, APO E, APO CI and APO CII] were determined and plasma levels of total homocysteine, total cholesterol (TC), triglycerides (TG), HDL-cholesterol (HLD-C) and apolipoproteins (apo A-I, Apo B, Apo E) were measured. RESULTS: Analysis of the four apolipoprotein gene polymorphisms shows a relative genetic homogeneity between Tunisian population and those on the other side of Mediterranean basin. Compared to controls, CAD patients have significantly higher main concentrations of TC, TG, LDL-C, apo B and homocysteine, and significantly lower ones of HDL-C, apo A-I and apo E. The four apolipoprotein gene polymorphisms have not showed any significant differences between patients and controls. However, the APO E4 allele appears to be associated to the severity of CAD and to high levels of atherogenic parameters and low level of apo E, which has very likely an anti-atherogenic role. CONCLUSION: Although APO (a) PNR, APO CI and APO CII genes are analyzed in only few populations, they show a frequency distribution, which is not at variance with that of APO E gene and other widely studied genetic markers. In the Tunisian population the APO E 4 appears to be only indirectly involved in the severity of CAD. In the routine practice, in addition of classic parameters, it will be useful to measure the concentration of apo E and that of Homocysteine and if possible to determine the APO E gene polymorphism.