Genetic relationships among Berbers and South Spaniards based on CD4 microsatellite/Alu haplotypes.

BACKGROUND: CD4 STR/Alu haplotype diversity, both for its qualitative and quantitative properties, has been widely used in molecular anthropology to clarify the degree of genetic relationships among human populations. AIM: CD4 STR/Alu variation was studied in two West Mediterranean samples, Andalusians from La Alpujarra region on the north side of the Gibraltar Strait and Berbers from the south, to ascertain the pattern of affinities between them. SUBJECTS AND METHODS: Alu and microsatellite alleles were tested in 99 Andalusians from La Alpujarra region (Southeast Spain) and 124 Middle Atlas Berbers (Morocco). RESULTS: Two new combinations of Alu and STR alleles (75(+) and 80(-)) were found in Berbers. The CD4 STR/Alu haplotype distribution in South Spaniards is similar to that of other Europeans, the only special feature is the slight presence of the 90(+) and 130(+) typical Sub-Saharan haplotypes. The Berber sample is characterized by a high number of different haplotypes (18) with intermediate heterozygosity values (0.846) in comparison with other North African groups, and by a high frequency of the 110(-) combination that has been proposed as representative of an ancient Northwest African population. CONCLUSION: A geographical gradient of Sub-Saharan gene contribution has been detected in North Africa. The Middle Atlas Berbers showed an intermediate value in comparison with the high and low values found in Mauritanians and Moroccan Berbers, respectively. The analysis of the CD4 STR/Alu haplotype variation failed to indicate any particular relationship between South Spaniards and North Africans.

Apolipoproteins E and C1 and brain morphology in memory impaired elders.

Previous research has shown that polymorphisms of the apolipoproteins E ( APOE) and APOC1 represent genetic risk factors for dementia and for cognitive impairment in the elderly. The brain mechanisms by which these genetic variations affect behavior or clinical severity are poorly understood. We studied the effect of APOE and APOC1 genes on magnetic resonance imaging measures in a sample of 50 subjects with age-associated memory impairment. The APOE E4 allele was associated with reduced left hippocampal volumes and APOE*E3 status was associated with greater frontal lobe white matter volumes. However, no APOE effects were observed when analyses accounted for other potential confounding variables. The effects of APOC1 on hippocampal volumes appeared to be more robust than those of the APOE polymorphism. However, no modulatory effects on brain morphology outside the medial temporal lobe region were observed when demographic variables, clinical status, and other anatomical brain measurements were taken into consideration. Our results suggest that the role of the APOC1 polymorphism in brain morphology of the cognitively impaired elderly should be examined in further studies.

Classical polymorphisms in Berbers from Moyen Atlas (Morocco): genetics, geography, and historical evidence in the Mediterranean peoples.

BACKGROUND: Mediterranean population relationships have recently been reviewed through the analysis of classical and DNA markers. The differentiation between Berbers and Arabic-speakers to the south, and the genetic impact of the seven centuries of Muslim domination in the Iberian Peninsula have been among the most interesting questions posed in these studies. AIM: The present study seeks to assess the degree of genetic affinity between the two main population groups of Morocco: Berbers and Arabic-speakers. Data from the Berber study population were also compared with published information on 20 circum-Mediterranean groups. SUBJECTS AND METHODS: A Berber sample of 140 individuals from Moyen Atlas (Morocco) has been characterized using 15 classical markers (ABO, Duffy, MNSs, Rh, ACPl, AKl, ESD, GLOI, 6-PGD, PGMl, GC, HP, PI, PLG and TF). RESULTS: Allele frequencies in the Berbers fit well into the general southern Mediterranean ranges, albeit with some peculiarities, such as the high FY*A, ACPl*C, and PI*S values. The general pattern of relationships among Mediterranean peoples tested by genetic variance analysis was compatible with a north-south geographical differentiation. Spatial auto-correlation analysis in the different geographical regions of the Mediterranean reveals that the highest degree of association between allele frequencies and geographical distances corresponds to the western (41% of significant correlograms) and northern Mediterranean populations (33%). When only southern Mediterranean groups were considered, the degree of geographical structure considerably decreases (11% of significant correlograms). CONCLUSIONS: The different loci studied revealed close similarity between the Berbers and other north African groups, mainly with Moroccan Arabic-speakers, which is in accord with the hypothesis that the current Moroccan population has a strong Berber background. Differences in the spatial pattern of allele frequencies also are compatible with specific population histories in distinct Mediterranean areas, rather than general population movements across the whole region.

Lack of association between methylenetetrahydrofolate reductase (MTHFR) C677T and ischaemic heart disease (IHD): family-based association study in a Spanish population.

The effect of the C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene, traditionally associated with ischaemic heart disease (IHD), was assessed in a Spanish population. The transmission disequilibrium test (TDT) was used to determine a possible association in a sample of 101 trios of IHD patients. The distribution of MTHFR genotypes was similar in the IHD subjects and the parental group; the TT genotype was present in 14.9% of IHD patients, as compared to 15.2% in the parents. The frequency of the T allele was also similar in IHD cases and parents (39.6% vs. 42.4%; p = 0.649). The TDT confirmed that the observed transmission of the T allele did not deviate significantly from the expected one (chi2 = 0.743; p > 0.4). Our TDT analysis clearly demonstrates a lack of association between the T allele of the C677T mutation in MTHFR and cardiovascular artery disease, both for the general group and for different risk subgroups (smokers, hypertension, male sex, overweight and type A behaviour pattern) in the Spanish population.

Apolipoprotein molecular variation in Moroccan Berbers: pentanucleotide (TTTTA)n repeat in the LPA gene and APOE-C1-C2 gene cluster.

Apolipoprotein LPA, APOE, APOC1, and APOC2 genotype frequencies have been determined for the first time in a North African population. A sample of 140 Berber individuals from the Moroccan Moyen Atlas region has been analyzed. Allelic and haplotypic data have been used to compare our sample with other world populations and the results clearly differentiate Berbers from Europeans and Sub-Saharans, suggesting several distinctive features of Moroccan Berbers as the extreme high values of LPA PNR*11 pentanucleotide allele (10.5%) and the relatively high and low values of APOE*E4 (15.7%) and *E2 (4.5%) in comparison to other Mediterraneans. Another remarkable result is the frequency distribution of the two APOC2 alleles (70% vs 30%) in comparison with the European pattern (50% of each allele). The high values of APOE*E4 and LPA PNR*7 together with the intermediate linkage disequilibrium values between APOE and APOC1 alleles in comparison with Europeans and Africans suggest a certain degree of Sub-Saharan influence in the current Moroccan population.

Relation of Apo E and ACE genes to cognitive performance in chronic alcoholic patients.

Apolipoprotein E epsilon4 and ACE genes have been related to several conditions involving cognitive impairment, including Alzheimer's disease, normal ageing and cerebrovascular disease. However, it has not been established whether their genotypes are associated with alcoholism or its cognitive functioning. Genotypic distributions of 140 chronic alcoholic patients were compared with a non-alcoholic sample, and the cognitive performance of a subsample of the alcoholic subjects was assessed with standard neuropsychological tests. No differences in allele or genotype distributions of Apo E or ACE genes were found when comparing controls and alcoholics (Apo E epsilon2/2; patients 1.4%, controls 0% p < 0.06; epsilon2/epsilon3; patients 9.3%, controls 6.6% p < 0.29; epsilon2/epsilon4; patients 0%, controls 1% p < 0.31; epsilon3/epsilon3 patients 71.4%, controls 72% p < 0.89; epsilon3/epsilon4; patients 15.7%, controls 19.2%, p < 0.36; epsilon4/epsilon4; patients 2.1%, controls 1.2% p < 0.44; ACE D/D; patients 35%, controls 28.5% p < 0.14; I/D; patients 47.5%, controls 51.1% p < 0.51; I/I; patients 14.5%, controls 20.4% p < 0.19). In terms of cognitive performance, epsilon4/epsilon3 patients did better on visuoconstructive (p < 0.001) and visual memory (p < 0.04) functions compared with epsilon2/epsilon3 bearers. Furthermore, ACE D/D patients performed better on a test of abstract reasoning (p < 0.03) compared with the ACE I/I homozygous group. The cognitive results suggest that Apo E or ACE genotypes may modify the effects of ethanol on cognitive deterioration in alcoholic patients. However, the data do not support an association between the Apo E epsilon4 allele and reduced cognitive performance in alcoholism.

APOE and APOC1 genetic polymorphisms in age-associated memory impairment.

We studied the distribution of two genetic polymorphisms (APOE and APOC1) in a sample of 100 subjects fulfilling the NIMH criteria for age-associated memory impairment (AAMI) and 124 controls. We found significant associations both for APOE and APOC1 loci and their combinations with the AAMI condition. The findings in our sample suggest that memory-impaired subjects as described by the NIMH may be genetically differentiated from normally aging subjects in relation to these two polymorphisms and indicate the interest of considering variations in the APOC1 gene for further studies in cognitive aging.

Neuropsychological and genetic differences between age-associated memory impairment and mild cognitive impairment entities.

OBJECTIVE: To neuropsychologically and genetically compare age-associated memory impairment (AAMI) and mild cognitive impairment (MCI) entities and to determine what proportion of AAMI diagnosed individuals could also receive a MCI diagnosis. To compare the distribution of a previously known genetic risk factor for Alzheimer's disease (apolipoprotein E common polymorphism) associated with these two conditions with a sample of the normal aging. DESIGN: Neuropsychological and genetic assessments in AAMI and MCI individuals. Genetic assessment in AAMI, MCI, and control subjects. SETTING: General health centers and geriatric homes from northeastern Spain (Catalunya). PARTICIPANTS: One hundred and four subjects presenting subjective memory complaints were selected and the AAMI and MCI criteria were applied. One hundred and twenty-four healthy Spanish subjects age 50 and older were defined as controls. MEASUREMENTS: Memory, language, and frontal lobe functions were assessed using standard neuropsychological tests. The apolipoprotein E (apo E) polymorphism was obtained by using polymerase chain reaction (PCR) and HhaI restriction endonuclease. RESULTS: Sixty-seven percent of previously diagnosed AAMI individuals could also be identified as MCI subjects. These MCI cases differed from those only-AAMI individuals both in neuropsychological and genetic analyses, performing worse not only on memory but also on language and frontal lobe tests and presenting high and low prevalences of the apo E epsilon 3/epsilon 4 and epsilon 3/epsilon 3 genotypes, respectively. The general AAMI sample of 93 individuals also differed from controls in the apo E genotype and allele distributions but these differences were no longer present after subtracting the MCI cases (63 subjects). These findings reflect that the differences between the memory impaired sample and the control sample regarding the apo E polymorphism were mainly attributable to MCI individuals and not to those who received only a diagnosis of AAMI alone. CONCLUSIONS: Our findings suggest that among AAMI subjects, those who also fulfill the MCI criteria present a neuropsychological and genetic profile closer to that previously related to Alzheimer's disease than those individuals only eligible for a diagnosis of AAMI. However, our findings also suggest that using only the AAMI criteria still appears to select a population that differs genetically from the normal older population.

MRI and genetic correlates of cognitive function in elders with memory impairment.

The present study investigated the relationship between genetic variation, MRI measurements and neuropsychological function in a sample of 58 elders exhibiting memory decline. In agreement with previous reports, we found that the epsilon4 allele of the apolipoprotein E (APOE) and the D allele of the angiotensin converting enzyme (ACE) polymorphisms negatively modulated the cognitive performance. Further, we found an association between the A allele of the apolipoprotein C1 (APOC1) polymorphism and poorer memory and frontal lobe function. No clear associations emerged between MRI measures of white matter lesions (WML) or hippocampal sulcal cavities (HSC) and the cognitive performance after controlling for age effects. Further, the degree of WML or HSC lesions was in general not predisposed genetically except for the presence of the A allele of the APOC1 polymorphism that was related to a higher severity of HSC scores. Our results suggest that WML or HSC do not represent important brain correlates of genetic influences on cognitive performance in memory impaired subjects.

Angiotensin I converting enzyme polymorphism in humans with age-associated memory impairment: relationship with cognitive performance.

We compared the distribution of an insertion (I)/deletion (D) polymorphism coding for the angiotensin I converting enzyme (ACE) gene in 100 subjects fulfilling NIMH criteria for Age-associated memory impairment (AAMI) and 124 controls. We found significantly reduced prevalences of the ACE I/I genotype together with increases of the ACE D allele in the AAMI group. We further compared the neuropsychological performance of the AAMI group according to their ACE genotype. Those AAMI subjects presenting the ACE I/I genotype exhibited better performance on a measure of frontal lobe function. Our results suggest that the lack of the ACE I/I genotype and the presence of the ACE D allele are associated with memory impairment in the elderly.