Relationship between proinflammatory cytokines (Il-1beta, Il-18) and leukocyte telomere length in mild cognitive impairment and Alzheimer's disease.

Inflammation plays a crucial role in Alzheimer's disease (AD). AD neurodegeneration and concurrent involvement of the peripheral immune system may promote leukocyte division and telomere shortening. We examined genotypes and plasma levels of two proinflammatory cytokines, IL-1beta and IL-18, and leukocyte telomere length (LTL) in patients with mild cognitive impairment (MCI) and AD. We wanted to determine whether changes in plasma IL-1beta and IL-18 levels, together with LTL shortening, could be diagnostic for disease progression from MCI to AD. Median plasma IL-1beta levels were in the order MCI patients (2.2 pg/ml) < AD patients (4.0 pg/ml), both of which differed significantly from the controls (0.0 pg/ml). In the AD patients, the lowest IL-1beta levels were associated with the presence of the C allele of IL-1beta rs16944 SNP. Median plasma IL-18 levels were in the order MCI patients (116.3 pg/ml) > AD patients (85.8 pg/ml), both of which were significantly higher than in the controls (17.6 pg/ml). Analysis of LTL showed a progressive reduction in the order controls > MCI > AD patients (p < 0.0001). Overall LTL reduction was correlated with increased plasma IL-1beta levels, substantiating the hypothesis that inflammatory processes secondary to neuroinflammation may trigger telomere attrition. Changes in plasma IL-1beta and Il-18 levels, and LTL seem to reflect shifts in AD stage; they may have potential use as blood biomarkers to monitor disease onset and progression from MCI to AD.

Modulation of Inflammation as a Way of Delaying Alzheimer's Disease Progression: The Diet's Role.

BACKGROUND: Most of the recent reports suggest that inflammatory mediators play a central role in the etiopathogenesis of Alzheimer's disease (AD) and that the conditions leading to a chronic low-grade inflammation, such as stress, depression, obesity and metabolic syndrome, increase the odds of developing Mild Cognitive Impairment (MCI) and AD. Microglia cells are the main actors in the AD process: stimuli from the microenvironment may induce microglia cells to switch to a classically activated inflammatory phenotype M1, or, on the contrary to an alternatively activated M2 phenotype characterized by the secretion of different types of cytokines. Many attempts are currently being made in order to delay the progression of AD by reducing inflammatory mechanisms underlying the disease. Several studies support a relationship among neuroinflammation and nutrients, foods or dietary patterns, taking into account the synergistic or antagonistic biochemical interactions among nutrients as well as the different food sources of the same nutrient. Natural antioxidant and anti-inflammatory compounds found in plant foods, such as fruits, particularly berries (such as strawberry, blueberry, blackcurrant, blackberry, blueberry and mulberry) have been shown to exert neuroprotective activity. It is still unclear whether the dietary bioactive compounds enter the Blood Brain Barrier (BBB) playing a direct antiinflammatory or pro-inflammatory effect on microglia and/or other Central Nervous System (CNS) cells. Another hypothesis is that they may trigger a peripheral reaction that induce indirectly a CNS' response. The subsequent synthesis of cytokines may drive microglia polarization by different ways. So, via an indirect route microglia detects and responds to immune-to-brain signaling. CONCLUSION: This review summarizes current evidence about the potential mechanisms of the interaction among diet, neuroinflammation and AD.

Common variants of human TERT and TERC genes and susceptibility to sporadic Alzheimers disease.

Studies investigating telomere length in association with cognitive decline, dementia, and sporadic Alzheimer's disease (AD) have frequently found shorter telomeres to be associated with the development of AD and telomerase expression with pathological processes in AD. Human telomerase is constituted by two components: the telomerase reverse transcriptase (TERT) and the telomerase RNA component (TERC). Genetic variation at the two loci has been investigated in relation to telomere length, longevity, and common diseases of advanced age, but not in relation to AD. We examined three polymorphisms of the TERT gene (VNTR MNS16A, rs2853691, rs33954691) and three polymorphisms of the TERC gene (rs12696304, rs3772190, rs16847897) in a sample of 220 AD patients and 146 controls. MNS16A LL genotype was found to be associated with an increased risk of AD only in males [interaction term adjusted OR=3.55 (95% CI 1.2-10.2)]. The three TERC single nucleotide polymorphisms are in strict linkage disequilibrium and their genotype combinations influenced the age at AD onset (AAO). The combined genotype GG-TT-CC was associated with a mean AAO six years lower (70.5±6.7) than that associated with the other genotype combinations (76.04±6.7, p=0.01). The fact that the MNS16 L allele has been reported to lower TERT expression, and that the TERC alleles G, T, C (rs12696304, rs3772190, rs16847897 in this order have been repeatedly found associated with shorter LTL, seems to corroborate the hypothesis of a role of telomere length and telomerase in AD susceptibility.

P21 gene variation and late-onset Alzheimer's disease in the Italian population.

BACKGROUND: Variation at the cyclin-dependent kinase inhibitor gene P21 in a patient sample of the Italian population was investigated in search of genetic factors potentially involved in sporadic late-onset Alzheimer's disease (AD). METHODS: Two single nucleotide polymorphisms (SNPs) were studied in this gene: a C>A transversion at codon 31 (ser>arg) in exon 2 (RS1801270) and a C>T transition occurring 20 bp downstream from the stop codon of exon 3 (RS1059234). RESULTS: The odd ratios were: RS1801270 A allele = 0.62 (95% CI = 0.33-1.18; p = 0.14); RS1059234 T allele = 0.57 (95% CI = 0.33-0.98; p = 0.04). In addition, a longer duration of disease was found with genotypes carrying the RS1059234 T allele (4.3 ± 2.5 years) than with those not carrying it (3.3 ± 2.1 years) (p = 0.001). CONCLUSION: In the present sample, one of the two SNPs seems in some way related to AD, since carriers of one allele were slightly protected against AD onset.

Are apolipoprotein E alleles correlated with semen quality?

Apolipoproteins have a unique role in lipoprotein metabolism regulation, aiding lipid transport and acting as a cofactor of the enzymes involved in metabolism. There are three co-dominant alleles, APOE*2, APOE*3 and APOE*4, which encode three protein isoforms, apoE2, apoE3 and apoE4. APOE*3 is the most frequent in all populations thus far investigated, ranging from 50 to 90%. Some studies have tried to resolve a genetic 'dilemma' by evaluating the cause of the frequency and survival of the three alleles. Genetic drift, migration or natural selection could explain the current distribution of APOE gene frequencies worldwide. If APOE*4 is the ancestral allele, APOE*3 must have offered a considerable selective advantage, perhaps consisting of a positive effect during the reproductive period. Given this, there is a need to understand if APOE gene polymorphism might affect reproductive capacity. Few studies have been conducted in this area, and they generally correlate APOE polymorphism with reproductive efficiency in terms of number of children. The aim of our study was to look for correlations between APOE polymorphism in humans and semen quality, to establish if APOE genotypes have any demonstrable effect on spermatogenesis. In conclusion, our data show that APOE polymorphism is not associated with semen quality, as it is present to a similar extent in both normal and impaired or absent spermatogenesis. This demonstrates once again that the use of number of children as an index of fertility is not indicative of real male reproductive capacity.

Association of ACE I/D polymorphism and recurrent miscarriages in an Italian population with a pre-modern reproductive pattern.

Angiotensin I-converting enzyme (ACE), in addition to its role in the renin angiotensin system, has a physiological function in the fibrinolysis pathway, the accurate control of which is critical for the normal development of pregnancy. Recently, the ACE I/D polymorphism was found to be associated with recurrent spontaneous miscarriages (RM). The present study analysed the relationship between ACE I/D polymorphism and the number of spontaneous miscarriages, the number of pregnancies and the number of children in a sample of 88 Italian women born before 1930, with a pre-modern reproductive behaviour. The ACE DD genotype was more prevalent among women with RM (p = 0.02). However, the women carrying the DD genotype not only had the highest number of miscarriages (p = 0.03), but also the highest number of pregnancies with an eventual complete fertility (children no = 4.4), similar to that of women carrying the other ACE genotypes. In contrast, published data on contemporary women with RM seem to indicate that the DD genotype could now be associated with a reduced reproductive success compared to the other ACE genotypes. It is suggested that this phenomenon may be the effect of the interaction between ACE genotypes and contemporary reproductive behaviours (delay in childbearing, below-replacement fertility).

Estrogen receptor alpha polymorphisms and fertility in populations with different reproductive patterns.

The estrogen receptor (ER) plays an important role in mediating estrogen action on target tissues. ER-alpha, the most abundant, is found in all human reproductive tissues and studies on alpha-ER knockout mice have highlighted its role in reproduction. ER-alpha gene (ESR1) polymorphisms have been associated with a variety of disorders including human infertility. In this study, we examined the association of ESR1 PvuII and XbaI polymorphisms with fertility in two populations with different reproductive patterns and precisely in a sample of healthy Italian men and women (n=178) and in a sample of healthy African-Ecuadorian women (n=57). ESR1 xx and ppxx genotypes among the Italian men were found to be associated with an above-median number of children (P=0.01 and P=0.004, respectively). ESR1 pp genotype among the Italian women showed a tendency to be associated with a lower number of abortions (P=0.04), whereas ESR1 pp and ppxx genotypes among African-Ecuadorian women were associated with a higher number of children (P=0.02 and P=0.03, respectively). These results are consistent with previous observations indicating a role of ESR1 genotypes in human infertility and give insight into the complex interactions between genotypes and reproductive behaviours in human populations.

An analysis of peroxisome proliferator-activated receptor gamma (PPAR-gamma 2) Pro12Ala polymorphism distribution and prevalence of type 2 diabetes mellitus (T2DM) in world populations in relation to dietary habits.

BACKGROUND AND AIM: The human peroxisome proliferator-activated receptor gamma (PPAR-gamma) is involved in lipid storage, glucose homeostasis and adipocyte differentiation. The Ala allele of the Pro12Ala polymorphism has been associated with a protective effect against T2DM. Ala allele frequencies are known for many populations, but data are absent for other interesting human groups. METHODS AND RESULTS: We examined samples from Ethiopia, Benin, Ecuador and Italy. In addition, we performed an analysis of the Pro12Ala polymorphism distribution in world populations, also in relation to T2DM prevalence and the diet lipid content. In the European populations, the Ala allele frequencies are distributed according to a latitudinal trend, with the highest in the northern and central European populations and the lowest in the Mediterranean populations. Considering the world populations, a significant inverse relationship between Ala frequency and T2DM prevalence was observed mainly in populations where energy from lipids exceeded 30% of the total energy intake. CONCLUSION: Northern Europe's cold climate has been hypothesised to have played a role in contributing to the present pattern. Moreover our analysis appears to confirm, at a population level, the protective effect of Ala allele against T2DM, already observed in case-control studies, but only in populations with a diet rich in lipids.

The missing ApoE allele.

The human apoE gene (APOE, GenBank accession AF261279) shows a common polymorphism, with the three epsilon2, epsilon3 and epsilon4 alleles resulting from the haplotypes of two C-->T SNPs. However, whereas the three common T-T, T-C and C-C haplotypes corresponding to the epsilon2, epsilon3 and epsilon4 alleles are well known, the last C-T haplotype (GenBank accession AY077451), encoding a fourth apoE allele, has rarely been reported. We detected this fourth allele in a Caucasian patient with motor neuron disease (MND). According to the literature we refer to this allele as epsilon3r. Although several explanations may be proposed for its formation, the existence of this fourth allele is consistent with the evolutionary hypothesis generally accepted for the apoE alleles. The rarity and physiological role of epsilon3r remains to be explained, and requires further investigation.

Apolipoprotein E polymorphism and fertility: a study in pre-industrial populations.

Human apolipoprotein E is the most important supplier of the cholesterol precursor for steroid hormone production in steroidogenic tissues and therefore could play a role in the regulation of steroid hormone function and influence human reproduction. This hypothesis has been confirmed by studies describing a differential fertility associated with common apolipoprotein (APOE) genotypes in two European populations. In the present investigation the impact of APOE genetic variation on fertility was studied in two Ecuadorian populations, African-Ecuadorians (57 women) and Cayapa Indians (27 women). In addition some biodemographic variables concerning women's fertility were investigated (124 African-Ecuadorian women; 40 Cayapa women) to better understand the APOE-fertility relationships in these pre-industrial populations. General fertility rates in both populations were very high (6.5 and 6.2 for the African-Ecuadorians and for the Cayapa respectively). When considering only women near the end of reproductive life (>/=40 years), a more marked difference was observed between the two groups (9.1 versus 7.7, P=0.09). In both communities, the highest number of children was found to be associated with the e*4/e*3 genotype; the e*4/e*3 genotype frequency (0.50) in the African-Ecuadorian women with 9-17 children was about three times that of the women with 0-8 children (0.14) (P=0.02). The present findings are at variance with those observed in European populations, where e*3/e*3 was the genotype associated with the highest reproductive efficiency. A possible explanation for this inconsistency could be due to the different functional properties associated with the e*3 and e*4 alleles and to genotype interactions with environmental factors including reproductive strategies.

New data on the world distribution of paraoxonase (PON1 Gln 192 --> Arg) gene frequencies.

The physiological role of human paraoxonase (PON), a serum enzyme that hydrolyzes organophosphate insecticides and nerve agents, is not clear. Of the three genes in the paraoxonase gene family, PON1 shows a polymorphism, Gln 192 --> Arg, governed by two common alleles named *Q and *R. These determine two different isoforms associated, respectively, with lower and higher activity towards paraoxon, a toxic metabolic product of the insecticide parathion. The *R allele has often been found associated with an increased risk of coronary heart disease. As human populations tend towards greater exposure to environmental changes, including changes in dietary habits and contact with insecticides or other toxic substances, health risks will change as well. In studying the prevention of these newly emerging risks, it could be important to know the distribution of the two alleles in the various world populations. In this paper we report on the genotype and allele frequencies of this polymorphism in different populations, most of which have never been examined for this polymorphism. Samples were taken from mainland Italy, Sardinia, Ethiopia, Benin, and Ecuador. The *R allele frequencies for the samples were: 0.313, 0.248, 0.408, 0.612, and 0.789, respectively. The data show a large variability in allele frequencies, and, in particular, that PON1 allele distribution depends on membership to different geographic populations.

Clinal patterns of human Y chromosomal diversity in continental Italy and Greece are dominated by drift and founder effects.

We explored the spatial distribution of human Y chromosomal diversity on a microgeographic scale, by typing 30 population samples from closely spaced locations in Italy and Greece for 9 haplogroups and their internal microsatellite variation. We confirm a significant difference in the composition of the Y chromosomal gene pools of the two countries. However, within each country, heterogeneity is not organized along the lines of clinal variation deduced from studies on larger spatial scales. Microsatellite data indicate that local increases of haplogroup frequencies can be often explained by a limited number of founders. We conclude that local founder or drift effects are the main determinants in shaping the microgeographic Y chromosomal diversity.

Genetic variation atapolipoprotein E locus in Ethiopia: an E5 variant corresponds to two different mutant alleles: E*5 (Glu212Lys) and E*5 (Gln204Lys; Cys112Arg).

A previous investigation on apolipoprotein E polymorphism in the Ethiopian population highlighted the presence of a further variant allele named E*5 in addition to the three common alleles. The variant is considered rare elsewhere but has a frequency of more than 1% in this population. Now characterized by gene sequencing and restriction isotyping in many members of the families of the original carriers, the variant isoform has actually been found to be determined by two different gene mutations. Effectively rare in Ethiopians, one of the two, E5 (Gln204Lys, Cys 112Arg), has never been described before. The other, E5 (Glu212Lys), previously described in a subject of Turkish origin, is present at the polymorphic level only in the Ethiopian population. No subjects bearing these variants had anomalous lipid or apolipoprotein patterns. In the course of the present investigation both have been found to occur as rare variants in the southern Italian population as well. The occurrence of the two variants in the populations of Ethiopia and of the Mediterranean basin could be explained by taking into account the relevant Caucasoid contribution to the Ethiopian gene pool.

Screening of two mutations at exon 3 of the apolipoprotein E gene (sites 28 and 42) in a sample of patients with sporadic late-onset Alzheimer's disease.

The search for further variation at the APOE gene in a sample of patients with sporadic late-onset Alzheimer's disease (AD) and related controls revealed two different mutations in the exon 3 of the gene. One, the Leu28-->Pro, always found on an APOE e(*)4 allele, was present in five of the 94 patients and in 1 of the 157 controls. The other, Thr42-->Ala, found on an e(*)3 allele, was observed in only one AD patient, who also carried the Leu28-->Pro, but in none of the controls. In the AD patient group the allele e(*)4(-), corresponding to Leu28-->Pro, showed a frequency of 0.027, compared with only 0.003 in the controls. Compared to E3/3 and E3/2 genotypes, the risk of developing AD associated with the genotypes carrying the e(*)4 allele, the well-established risk allele for AD onset, was observed to be high (OR=3.16; 95% CI=1.62-6.20; P=0.0009), but the risk associated with genotypes carrying the Leu28-->Pro mutation was higher still (OR=10.95; 95% CI=1.25-95.75; P=0.015). The higher risk associated with this mutation was assessed by meta-analysis carried out using the data of three patient groups from a previously published study Kamboh et al. and from our study. The results indicated that, compared with all the other APOE genotypes, those carrying the Leu28-->Pro mutation were at a substantially higher risk of developing AD (OR=4.25; 95% CI=1.21-14.97).

Plasma alpha1-antichymotrypsin in Alzheimer's disease; relationships with APOE genotypes.

Inflammatory processes are thought to be important contributors to the pathogenesis of Alzheimer's disease (AD). alpha1-antichymotrypsin (ACT) is a proteinase inhibitor characteristic of acute-phase inflammation and has been identified in amyloid plaques. We analyzed the plasma ACT levels in a sample of subjects with late-onset AD and correspondent controls. Plasma ACT was higher in AD patients (62.8 +/- 20.2 mg/dl) than in controls (58.8 +/- 18.1 mg/dl), but not significantly (P = 0.13). In the AD patients regression analysis showed a positive linear relationship between ACT levels and duration of the disease (P = 0.037). Increased ACT concentrations (64.6 +/- 21.2 mg/dl) were also found in patients with greater cognitive impairment (MMSE scores < 20), but since this factor depends on the duration of the disease as well, our present data seem to indicate a complex relationship involving elevated ACT levels, disease duration and cognitive impairment. Plasma ACT was found to differ significantly according to APOE genotypes (P = 0.017), the highest levels being associated to E3-E3 homozygotes (66.1 +/- 17.8 mg/dl) and the lowest to E4-E3 subjects (53.1 +/- 18.2 mg/dl). In patients not carrying APOE*4 allele the ACT levels were higher than in controls (P = 0.014), and the relationship between ACT and disease duration was stronger than that observed in the total AD sample (P = 0.003), but it was absent in those carrying APOE*4 (P = 0.67). Taken together our results seem to suggest that inflammation is a relevant factor in AD pathogenesis for subjects with E3-E3 and E3-E2 genotypes but less important for APOE*4 carrying subjects.

Polymorphisms in the apolipoprotein E gene regulatory region in relation to coronary heart disease and their effect on plasma apolipoprotein E.

In a previous study which examined the distribution of apolipoprotein E genotypes and plasma levels in a sample of male coronary heart disease (CHD) patients and controls, we found a significant excess of the genotypes carrying APOE*4 allele in CHD men (18.2%) vs. controls (9.6%) and an association between the APOE*4 allele and the lowest concentrations of apoE. In the present investigation, we re-examined in the same samples two recently identified polymorphisms in the promoter region of APOE, -491A/T and -427T/C, which may alter the level of apoE expression. No differences in the distributions of the -491A/T genotypes and alleles were observed between cases and controls (-491*A = 0.760 and 0.757 respectively). Polymorphism -427T/C showed in CHD patients an excess of -427*C allele (patients vs. controls = 0.123 vs. 0.074) and corresponding genotypes that was marginally significant. Stratification of the samples according to the presence/absence of APOE*4 showed that the excess of the -427*C allele concerned only CHD patients not carrying APOE*4 allele (patients vs. controls = 0.133 vs. 0.061; p=0.017). This result suggests that the presence of -427*C allele could represent a risk for developing CHD in subjects with E2/E2, E3/E2, and E3/E3 genotypes. Studies carried out on patients with Alzheimer's disease demonstrated that -491A/T and -427T/C polymorphisms affect the level of plasma apoE. In the present study, carried out on CHD patients and controls, the genetic variation at -427 and -491 sites of the APOE regulatory region had no apparent effect on apoE plasma concentration.

Polymorphisms of the apolipoprotein E gene regulatory region and of the LDL receptor gene in late-onset Alzheimer's disease in relation to the plasma lipidic pattern.

Two new polymorphisms in the regulatory region of the apolipoprotein E gene, -491 A/T and -427 T/C, have been reported to be associated with the risk of Alzheimer's disease (AD). Moreover, in vitro studies suggest that the two polymorphisms modulate the levels of apoE protein expression. We examined these two polymorphisms, as well as the MspI polymorphism in the LDL receptor gene, in a series of elderly patients with late-onset sporadic AD and in an age-matched control group but failed to find any kind of association between these genetic features and an increased risk of AD. In the same samples we investigated the relationships between various genotypes and plasma lipid levels. Since the well-known effect of the three-allelic APOE polymorphism on plasma lipid levels could mask the effect of other polymorphisms, the analyses were performed taking into account the APOE genotype. The two regulatory region polymorphisms had significant effects only on the apoE levels. The -427 TT homozygotes had lower, and the -491 AA homozygotes had higher levels of apoE than other genotypes. This result confirmed in vivo the already observed in vitro effects of -491 A/T and -427 T/C polymorphisms on APOE promoter transcription activity.

Latitude-correlated genetic polymorphisms: selection or gene flow?

Latitude-correlated polymorphisms can be due to either selection-driven evolution or gene flow. To discriminate between them, we propose an approach that studies subpopulations springing from a single population that have lived for generations at different latitudes and have had a low genetic admixture. These requirements are fulfilled to a large extent by Ashkenazi and Sephardi Jews. The original population lived at a latitude of 35 degrees N, where the Sephardis still live. The Ashkenazis, however, moved to a latitude of 50 degrees N, starting about 10 centuries ago. The present study examines 3 latitude-correlated polymorphisms: PGP, PGM1, and AHSG. We found that PGP*2 and AHSG*2 alleles most likely underwent selection-driven evolution, but that PGM1*ts allele was not similarly affected. Since temperature might have been considered a reasonable selective factor, we also studied a population living at >800 m above sea level from Aosta Valley (Italy).

Apolipoprotein B, apolipoprotein E, and angiotensin-converting enzyme polymorphisms in 2 Italian populations at different risk for coronary artery disease and comparison of allele frequencies among European populations.

Polymorphisms at the apolipoprotein B (APOB XbaI, EcoRI, insertion-deletion), apolipoprotein E (APOE), and angiotensin-converting enzyme (ACE) loci are thought to be involved in susceptibility to coronary artery disease (CAD) and myocardial infarction. The aim of this study was to determine whether the allele distribution of the APOB, APOE, and ACE polymorphisms is different in 2 Italian regions with higher (northern Italy) and lower (Sardinia) CAD occurrence. The frequencies of the APOB and APOE alleles that are considered CAD risk factors were higher in northern Italy (APOB X- = 0.655; APOB R- = 0.198; APOB insertion = 0.757; APOE*4 = 0.110) than in Sardinia (APOB X- = 0.568; APOB R- = 0.159; APOB insertion = 0.680; APOE*4 = 0.052), although only APOE allele frequencies differed significantly (p = 0.001). ACE deletion allele frequencies in the 2 geographic areas showed an opposite pattern (northern Italy = 0.658; Sardinia = 0.721). Furthermore, we investigated the impact of APOB and APOE polymorphisms on interindividual variation in total cholesterol level in the 2 Italian samples, which differ in dietary habits. Only APOE phenotypes showed different mean levels of total cholesterol; the association was significant only in northern Italy (p = 0.04), where continental dietary habits and higher mean cholesterol levels prevail. These results support the suggestion that the cholesterol increasing effect of APOE*4 is environmentally mediated. Analysis of allele distributions among European populations, with remarkable differences in CAD prevalence, revealed a constant positive relationship between APOE*4 allele frequency and CAD incidence. The highest frequencies of APOB X- and R- were observed in Finland, where the incidence of CAD is high, and there is a partial agreement between APOB R- frequency and CAD occurrence across Europe, while APOB insertion and ACE deletion alleles are evenly distributed among European populations.

Genetic population structure of two African-Ecuadorian communities of Esmeraldas.

The genetic structure of two African-Ecuadorian communities, Rio Cayapas and Viche (Esmeraldas province, northwest Ecuador), was studied on the basis of ACP1, ADA, AK1, CA2, ESD, GLO1, G6PD, PGD, and PGM1 subtypes and thermostability, PGM2, HBbeta, F13A, F13B, ORM1, AHSG, C6, C7, and APOC2 gene frequency, and migration data on 255 individuals. The fixation index of Wright (F(ST)), correspondence, and genetic distance analysis were applied to compare the genetic relationships between these communities and other American populations of African ancestry. F(ST) values from the migration data and surname origins suggest that Rio Cayapas is genetically more isolated and shows less mobility and admixture than does Viche. The genetic admixture estimates indicate a large contribution of African genes to the gene pool of both communities (74.3% to 58.4%), whereas the proportion of the Amerindian component differs significantly (14.5% in Rio Cayapas to 27.6% in Viche).