High frequencies of short alleles of NOS1 (CA)n polymorphism in beta(0)39 carriers from Corsica Island (France).

In this work we investigated about the presence of a correlation between a (CA)n repeat located in exon 29 of NOS1 gene and the beta-thalassemia trait in Corsica Island (France). We genotyped a sample of individuals with beta-thalassemia minor (N=110) and an ethnically matched control (N=113) from Balagna, a region of Corsica Island (France). Results highlighted the high frequencies of allele with 16 and 17 repeats in the thalassemic sample. From these results we suggest, that high frequencies of alleles with 16 and 17 repeats, could be a consequence of past malarial endemicity.

Dual infections by influenza A/H3N2 and B viruses and by influenza A/H3N2 and A/H1N1 viruses during winter 2007, Corsica Island, France.

BACKGROUND: The investigation of dual influenza infection human cases is of major interest specifically for the control of new emerging influenza strains. OBJECTIVES: Using RT-PCR assays, we retrospectively assessed the prevalence of dual influenza virus infections that occurred in patients during the 2006-2007 winter season in Corsica Island (France). STUDY DESIGN: One hundred and thirty-four nasal swabbing samples taken from patients suffering from influenza-like illness between February and March 2007 were analysed using a rapid influenza antigen detection test, cell culture and RT-PCR assays. RESULTS AND CONCLUSION: Influenza viruses were detected in 93 (69.4%) of 134 patients with influenza-like illness using the combination of classical and molecular assays. Dual respiratory infections by influenza viruses were detected in 3 (3.2%) of the 93 influenza positive patients, including two cases of infection by influenza A/H3N2 and B viruses and one case of dual infection by influenza A/H3N2 and A/H1N1 viruses. In the present report, human co-infection cases by two influenza viruses appeared as a rare event in symptomatic patients. However, the virological and epidemiological mechanisms that determine the occurrence of dual influenza infections remain to be fully investigated in further prospective multicentric studies.

Photoaffinity labeling of membrane-bound porcine aminopeptidase N.

To investigate the possible role of aminopeptidase N (alpha-aminoacyl-peptide hydrolase (microsomal), EC 3.4.11.2) in the transport of amino acids from oligopeptides, the modified amino acids Phe(N3) and Phe(N3, I) and the tetrapeptides Phe(N3) or Phe(N3, I)-L-or-DAla-Gly-Gly have been synthesized. The azido-amino acids were radioactively labeled by tritium or 125I before their coupling with the tripeptides. Their utilization as photoaffinity labels for aminopeptidase N has been studied. The modification imposed at the N-terminal residue of the tetrapeptides has not impaired their hydrolysis by porcine aminopeptidase N (same kinetic parameters as unmodified peptides). In addition, evidence is presented for a specific and reversible interaction in the dark of the azido-derivatives at the substrate recognition site of the enzyme. Upon photolysis, irreversible inactivation of aminopeptidase N and covalent attachment of Phe(N3, I) have been demonstrated. Soluble and membrane-bound aminopeptidases are both labeled to the same extent indicating that the free azido-amino acid preferentially reacts with the external part of the enzyme. Although the linkage of the azido-derivative is not strictly restricted to the region of the active site, the values obtained strongly suggest that 1 mol probe has been covalently attached per mol monomer of inhibited aminopeptidase.

Human Y-chromosome variation in the western Mediterranean area: implications for the peopling of the region.

Y-chromosome variation was analyzed in a sample of 1127 males from the Western Mediterranean area by surveying 16 biallelic and 4 multiallelic sites. Some populations from Northeastern Europe and the Middle East were also studied for comparison. All Y-chromosome haplotypes were included in a parsimonious genealogic tree consisting of 17 haplogroups, several of which displayed distinct geographic specificities. One of the haplogroups, HG9.2, has some features that are compatible with a spread into Europe from the Near East during the Neolithic period. However, the current distribution of this haplogroup would suggest that the Neolithic gene pool had a major impact in the eastern and central part of the Mediterranean basin, but very limited consequences in Iberia and Northwestern Europe. Two other haplogroups, HG25.2 and HG2.2, were found to have much more restricted geographic distributions. The first most likely originated in the Berbers within the last few thousand years, and allows the detection of gene flow to Iberia and Southern Europe. The latter haplogroup is common only in Sardinia, which confirms the genetic peculiarity and isolation of the Sardinians. Overall, this study demonstrates that the dissection of Y-chromosome variation into haplogroups with a more restricted geographic distribution can reveal important differences even between populations that live at short distances, and provides new clues to their past interactions.

Mitochondrial control-region sequence variation in the Corsican population, France.

The mtDNA sequence variation of the hypervariable segment I of the control region was studied in 47 unrelated individuals of Corsican origin from Corte (Corsica, France). Thirty-one different sequences were identified by 40 variable sites, of which five involve transversions. The nucleotide diversity among the sequences was estimated as 1.03%. The pairwise difference agreed with the model proposed by Rogers and Harpending ([1992] Mol Biol Evol 9:552-569) and appeared bell-shaped, with only one peak at 3.71, indicating the occurrence of a single episode of demographic expansion roughly 14,443 to 41,584 years ago. From our results it seems that the ancestral Corsican population expanded more recently than all other studied European populations. Compared to other populations by genetic distances and a neighbor-joining tree, Corsicans appear most closely linked to the Basques and Sardinians than to other populations. Although the results substantiate an east-to-west migration, some problems are evident: 1) the estimates of demographic expansion are not in agreement with paleontological data; 2) the expansion occurred later than the expansion of the Sardinian population; and 3) the genetic affinity between Corsicans, Basques, and Sardinians. Answers will need to come from archaeological, paleontological, genetic, geological, and climatological observations. Finally, the study of mtDNA confirms what had already been shown with classic genetic markers. Am. J. Hum. Biol. 12:339-351, 2000. Copyright 2000 Wiley-Liss, Inc.

Genetic structure of southwestern Corsica (France).

The distribution of nine red cell enzymes (ACP, ADA, AK, DIA, ESD, GLO1, PGM1, PGD, and SOD) and seven plasma proteins (C3, GC, HP, ORM, PI, PLG, and TF) was analyzed in a sample of 274 unrelated individuals from the southwestern area of Corsica (France), specifically from Ajaccio and nearby villages. The aim of the research was to study the genetic structure of Corsica and to add further to our knowledge about microgeographic variability of polymorphisms in Corsica. The analysis, carried out by genetic distances and R-matrix through 39 alleles of 13 genetic markers, reveals a certain degree of differentiation within Corsica. The results show a genetic heterogeneity between Corsica and other European and Mediterranean populations, although the genetic differences appear to be smaller between Corsicans and Sardinians than among Corsicans and other compiled populations. Am. J. Hum. Biol. 10:567-577, 1998. © 1998 Wiley-Liss, Inc.

The STR-based genetic profile of the population from Corsica island (France).

Short tandem repeats (STR) at loci HumFES/FPS, HumVWA, HumCSF1PO, HumTH01, HumFXIIIA01, HumTPOX, HumCD4, D3S1358 are markers of choice for population genetics and validated systems for forensic use. In this report, we analysed their allele frequency distribution in a sample of native blood donors from the two departments of Corsica island (France). Deviations from the Hardy-Weinberg rule and heterozygosity values consistently suggested a spatial differentiation of allele and genotype frequencies across the island. Pairwise comparisons showed that Corsican gene pool presents a high level of heterogeneity between departments and substantially differs from that of neighbouring and historically-related populations. The results suggest the use of local databases to calculate a priori statistics in human identity testing.

24 bp duplication of CHIT1 gene is not correlated with coronary artery disease in Corsica Island (France).

In this study we analyzed allele and genotype distributions of 24 bp duplication of the CHIT1 gene in a sample of patients (N=300) with coronary artery disease (CAD) and in a control group (N=300) from central Corsica (France), with the aim to investigate the possible association between CHIT1 genotypes and CAD in Corsican population. Serum chitotriosidase activity is increased in individuals experiencing an ischemic stroke of atherothrombotic etiology and in subjects with ischemic heart disease. Our results suggest that 24 bp duplication of CHIT1 gene is not correlated with CAD in Corsican population, according to a previous study carried out on a Spanish sample. Gene prevalence and perhaps gene-disease associations vary according to ethnicity. Further studies, based on different ethnic groups, could be suitable to determine the implication of this polymorphism with respect to CAD.

Cholesteryl ester transfer protein gene polymorphisms are associated with coronary artery disease in Corsican population (France).

The aim of the present study was to investigate the association between coronary artery disease (CAD) and Cholesterol Ester Transfer Protein (CETP) (gaaa)n polymorphisms of the CETP gene in Central Corsica island (France). The study group was composed by 300 unrelated Corsican patients with angiographically documented CAD and 300 unrelated healthy blood donors. Significant differences were observed in the distribution of CETP (gaaa)n alleles between the groups under study (p=0.03; chi(2): 16.8, df: 8). The occurrence of a long allele (408 bp) was higher in cases (12%) than in control group (2%), showing a 6.75-fold increased risk for CAD in Corsica patients (p=0.0055; OR=6.750; 95% CIs=1.47-31.00). The correlation of this polymorphism with the lipid profile (cholesterol, low density lipoprotein-cholesterol, high density lipoprotein-cholesterol and triglycerides) in the patients group was determined. There was a significant association of the long alleles of CETP (gaaa)n with HDL-C levels. In the patient and in the control groups the LL genotypes had lower HDL-C compared with the SS and SL genotypes (p<0.0001). In summary our results suggest that the genetic variation at the CETP gene may play an important role in determining CAD in Corsican population.

The ins and outs of population relationships in west-Mediterranean islands: data from autosomal Alu polymorphisms and Alu/STR compound systems.

The islands of the West Mediterranean have played a central role in numerous archaeological, historical and anthropological studies due to their active participation in the history of main Mediterranean civilisations. However, genetic data failed to fit in both their degree of internal differentiation and relationships. A set of 18 Alu markers and three short tandem repeats (STRs) closely linked to the CD4, F13B and DM Alu have been analysed in seven samples from Majorca, Corsica, Sardinia and Sicily to explore some of these issues. Our samples show a high genetic heterogeneity inside and among islands for the Alu data. Global differentiation among islands (F(ST) 2.2%) is slightly higher than that described for Europeans and North Africans. Both the estimated divergence times among samples and the high population heterogeneity revealed by Alu data are compatible with population differences since the first islands' settlement in the Paleolithic period. However, the high within-population diversities and the remarkable homogeneity observed in both STR and Alu/STR haplotype variation indicated that, at least since Neolithic times, gene flow has been acting in west Mediterranean. Genetic drift in west-coast Sardinia and gene flow in west Sicily have contributed to their general differentiation, whereas Corsica, Majorca and east Sicily seem to reflect more recent historical relationships from continental south Europe.

Genetic characterization of the historical Albanian ethnic minority of Calabria (southern Italy).

Three historical ethnic minorities are present in Calabria: Albanians, Greeks, and Occitans. The Albanian ethnic minority is the more populous, having settled in Calabria between the 15th and 17th centuries, and these populations are now located in the provinces of Cosenza and Catanzaro. In the present study the Albanian population structure is analyzed based on the allele frequencies of six classic genetic markers: ACP, GC, PGM1, AK, ADA, and 6PGD. The results show a significant heterogeneity between the Albanian population in Calabria and the population in Molise. Therefore the cultural and reproductive isolation of the Albanian ethnic minority of Calabria is related to a great genetic peculiarity. Moreover, the frequencies of some alleles, particularly those of the PGM*1W31 variant, and the analysis of the R matrix still show the actual peculiar genetic structure of the Albanians of Calabria, although the genetic flow is evident in the decrease of endogamy and in the increase in the degree of mixing.

Beta-globin cluster haplotypes in normal individuals and beta(0)39-thalassemia carriers from Sardinia, Italy.

Seven polymorphic sites in the beta-globin cluster in association with specific thalassemia mutations were analyzed in a sample from Sardinia, Italy. In order to verify previous works carried out on normal samples (beta(A)/beta(A)) and family studies on beta-thalassemia homozygotes individuals, the haplotype frequencies in both normal individuals (beta(A)/beta(A)) and beta(0)39-thalassemia carriers (beta(A)/beta0) were studied. In our work chromosomes carrying beta(0)39 mutation are characterized by a prevalence of haplotype II (- + + - + + +) (52%) relative to haplotype I (+- - - - + +) (29%), in contrast, among chromosomes with beta(A) the frequency of haplotype I is much greater than that of haplotype II. These data confirm what was found by other authors. Nevertheless, our results disagree with those of previous studies of Sardinians, both in frequencies values and in the numbers of haplotypes identified. Population analysis performed with samples carrying the beta-thalassemic mutation highlighted the peculiarity of Sardinians with respect to other Mediterranean populations. The Corsican population is most similar to the Sardinian population, confirming previous analyses performed with both classical markers and mitochondrial and genomic DNA.

Prevalence of genetic risk factors for coronary artery disease in Corsica island (France).

We have investigated the frequencies of seven markers among 100 unrelated individuals with angiographically documented CAD (Coronary Artery Disease) and among 100 unrelated healthy blood donors in the central region of Corsica island (France). The seven polymorphisms analyzed were chosen from six candidate genes involved in (1) Renin-Angiotensin system: Angiotensin converting enzyme (ACE I/D), (2) Lipid metabolism: Cholesterol Ester Transfer Protein gene (CETP TAQ1B), (3) Platelet aggregation: alpha and beta subunits of the platelet GpIIb/GpIIIa integrin complex (GpIIb HPA3 and GpIIIa Pl(A1/A2)), (4) Coagulation fibrinolysis: Plasminogen Activator Tissue (PLAT TPA25 I/D) and Methylenetetrahydrofolate Reductase (MTHFR C677T and A1298C). The samples were genotyped using the polymerase chain reaction followed by restriction enzyme analysis for the RFLPs. No significant difference in allele frequencies between patient and control groups was observed. The occurrence of the MTHFR T677T genotype and of the T677T/A1298A compound genotype is higher in cases (20%) than in the controls (4%). Odds ratio seems to indicate that individuals with the MTHFR T677T genotype and the T677T/A1298A compound genotype had a 6-fold increased risk for developing CAD (ORs = 6; 95% CIs = 1.96-18.28) suggesting a possible association of MTHFR C677T with the risk of CAD in Corsican population.

Studies on transport of amino acids from peptides by rat small intestine in vitro. Synthesis, properties and uptake of a photosensitive tetrapeptide.

By comparison with what is known of disaccharides transport, it has been suggested that intestinal aminopeptidase N could, hydrolyze, on the surface of the microvillus membrane, oligopeptides longer than tripeptides and itself subserve the translocation function for the amino acids released from these peptides. This article describes the synthesis of the tritiated azido-tetrapeptides p-azido[3H]phenylalanyl-alanyl-glycyl-glycine containing L or D-alanine. The synthesized products possess a function which displays all the characteristics of an aryl-azide. The photosensitive tetrapeptide formed with LAla-Gly-Gly is as good a substrate for porcine and rat aminopeptidases N as unmodified peptides while the tetrapeptide formed with DLa-Gly-Gly is not hydrolyzed at all. In addition a pattern of stepwise hydrolysis could be demonstrated and aminopeptidase N is the only exopeptidase present in the mucosal cells capable of utilizing the modified tetrapeptide as substrate. Uptake assays performed on everted rings of jejunum with the azido-tetrapeptide as substrate have shown that: (a) the azido-tetrapeptide is not transported intact but must be hydrolyzed first; (b) p-azido-phenylalanine is not released in the external medium and therefore its observed uptake is not from the bulk medium and (c) the azido-D-tetrapeptide is only accumulated by passive diffusion. These observations suggest the presence on the brush border membrane of an aminopeptidase-related transport system.

Oxidized LDL increase free cholesterol and fail to stimulate cholesterol esterification in murine macrophages.

Oxidatively modified low density lipoproteins (Ox-LDL) may be involved in determining the formation of foam cells by inducing cellular cholesteryl ester accumulation. We studied the effect of copper oxidized LDL (Ox-LDL) on cholesterol accumulation and esterification in murine macrophages. Ox-LDL (44 micrograms/ml of lipoprotein cholesterol) increased the total cholesterol content of the cells from 29 to 69 micrograms/mg cell protein. Free cholesterol accounted for 85% of this increase. Acetyl LDL (Ac-LDL) (38 micrograms/ml of lipoprotein cholesterol), raised total cellular cholesterol content to a similar extent (76 micrograms/mg cell protein), however only 25% of the accumulated cholesterol was unesterified. When ACAT activity was determined after incubation of J774 cell with Ox- or Ac-LDL, Ox-LDL were 12 times less effective than Ac-LDL in stimulating cholesteryl ester formation. This was not due to an inhibition of ACAT by Ox-LDL since these lipoproteins failed to inhibit pre activated enzyme in cholesteryl ester-loaded macrophages. The uptake of 125I-Ox-LDL: was 175% that of 125I-Ac-LDL, while degradation was only 20%. All together these data suggest an altered intracellular processing of Ox-LDL, which may be responsible for free cholesterol accumulation.

Mitochondrial DNA sequence analysis in Sicily.

This study reports data on the sequences of the first hypervariable segment of a sample of the Sicilian population from Alia (Palermo, Italy). The results show the presence of 32 different haplotypes in the 49 individuals examined. The average number of pairwise nucleotide differences was 4.04, i.e., 1.17% per nucleotide. The distribution of the nucleotide differences matches the theoretical distribution and indicates only one major episode of expansion that occurred between 20,732 and 59,691 years ago, between the Middle Paleolithic and Upper Paleolithic. Compared with the other populations, parameters of the Sicilian sample lie in an intermediate position between the eastern and western Mediterranean populations. This is due to numerous contacts that Sicily has had with the Mediterranean area since prehistoric times. At the same time, the singularity of some of the haplotypes present in the sample studied indicates the persistence of some characteristics caused by genetic drift and isolation that the population has endured in the course of its history.

Frequency distribution of mitochondrial DNA haplogroups in Corsica and Sardinia.

Mitochondrial DNA (mtDNA) polymorphisms were analyzed by polymerase chain reaction amplification and haplogroup-specific restriction screening in populations from Corsica and Sardinia. These included 56 individuals from the area of Corte, central Corsica (France), 51 individuals from Gallura, northern Sardinia (Italy), and 45 individuals from Barbagia, central Sardinia. The screening revealed that about 95% of mtDNAs could be grouped in 8 of the 9 European haplogroups, including H-K, T-V, and X. Our results confirmed that these haplogroups encompass virtually all the mitochondrial lineages present in Europe and can be detected in both northern and southern European populations. We also discovered 2 restriction sites (-73 Alw441 and +75 SphI) that allow the detection of informative nucleotide changes in the second hypervariable segment of the control region, which help to detect the haplogroup identity of mtDNAs without requiring further DNA sequencing. Haplogroup H was the most common mtDNA lineage in this sample, reaching frequencies from about 40% in Corsican and Gallurese populations, to about 65% in the Barbagian population. Haplogroup V, possibly originating in the Iberian peninsula, was found only in the central Sardinian sample. Of the 5 Corsican mtDNAs belonging to the haplogroup T, 4 had a restriction fragment length polymorphism found only in this population. It seems that this mutation originated in Corsica and has had time to spread in the area, since the maternal grandmothers of the subjects came from different villages of the island. The sample from central Sardinia shows a remarkable discontinuity with those from the northern part of the island and from Corsica. Gallura and Corsica seem to have undergone a more recent peopling event, possibly related to the arrival of new mitochondrial variability from continental Italy, while Barbagia has apparently maintained more archaic haplotypes.

Genetic structure and affinities of the Corsican population (France): classical genetic markers analysis.

The frequencies of 19 classical genetic markers for a total of 54 alleles were studied in a sample of 1,164 individuals born and residing in five different regions of Corsica. The results, which are also discussed in the context of the Mediterranean populations, show the existence within Corsica of a certain genetic differentiation between north and south which follows the linguistic subdivision differentiation. Compared to the other Mediterranean populations, Corsica also appears to be greatly differentiated from the populations of regions such as France and Tuscany, regions which have had great political and cultural influence. The Mediterranean population most comparable to Corsica is Sardinia. Despite their common origin, however, they do not prove to be absolutely identical. The genetic characteristics of Corsica and their relationship with the Mediterranean populations are interpreted in terms of demographic and matrimonial structure, isolation, and genetic drift.