Linkage disequilibrium at the ADH2 and ADH3 loci and risk of alcoholism.
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Two of the three class I alcohol dehydrogenase (ADH) genes (ADH2 and ADH3) encode known functional variants that act on alcohol with different efficiencies. Variants at both these genes have been implicated in alcoholism in some populations because allele frequencies differ between alcoholics and controls. Specifically, controls have higher frequencies of the variants with higher Vmax (ADH2*2 and ADH3*1). In samples both of alcoholics and of controls from three Taiwanese populations (Chinese, Ami, and Atayal) we found significant pairwise disequilibrium for all comparisons of the two functional polymorphisms and a third, presumably neutral, intronic polymorphism in ADH2. The class I ADH genes all lie within 80 kb on chromosome 4; thus, variants are not inherited independently, and haplotypes must be analyzed when evaluating the risk of alcoholism. In the Taiwanese Chinese we found that, only among those chromosomes containing the ADH3*1 variant (high Vmax), the proportions of chromosomes with ADH2*1 (low Vmax) and those with ADH2*2 (high Vmax) are significantly different between alcoholics and controls (P<10-5). The proportions of chromosomes with ADH3*1 and those with ADH3*2 are not significantly different between alcoholics and controls, on a constant ADH2 background (with ADH2*1, P=.83; with ADH2*2, P=.53). Thus, the observed differences in the frequency of the functional polymorphism at ADH3, between alcoholics and controls, can be accounted for by the disequilibrium with ADH2 in this population. (+info)
Knowledge, attitudes and practices during a community-level ivermectin distribution campaign in Guatemala.
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Community acceptance and participation are essential for the success of mass ivermectin chemotherapy programmes for onchocerciasis (river blindness). To explore the local understanding of the purpose of ivermectin and willingness to continue taking the drug, we performed questionnaire surveys in four communities with hyperendemic onchocerciasis after each of three ivermectin treatment rounds. More than 100 respondents participated in each KAP survey, representing the heads of 30% of the households in each community. The respondents rarely stated that the goal of the ivermectin treatment programme was to prevent visual loss. Instead, they said they were taking the drug for their general well-being, to cure the onchocercal nodule (filaria), or to cure the microfilaria, a term newly introduced by agents of the treatment programme. The principal reason identified for refusal to take ivermectin was anxiety about drug-related adverse reactions, and there were marked differences between communities in acceptance of treatment. In one community over 50% of residents initially refused to take ivermectin, although participation rates improved somewhat after programmatic adjustments. We recommend that ivermectin distribution programmes establish surveillance activities to detect where acceptance is poor, so that timely and community-specific adjustments may be devised to improve participation. (+info)
Risk factors for human T cell lymphotropic virus type II infection among the Guaymi Indians of Panama.
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To examine risk factors for human T cell lymphotropic virus type II (HTLV-II) infection, a case-control study was conducted among the Guaymi Indians of Panama. In females, HTLV-II seropositivity was associated with early sexual intercourse (15 years; odds ratio [OR], 2.50; 95% confidence interval [CI], 1.11-6.14) and number of lifetime sex partners. One partner increased risk of seropositivity by 30% (OR, 1.30; CI, 1.05-1.64), and risk increased with number of partners. Similar risk was associated with number of long-term sexual relationships. Among males, intercourse with prostitutes was associated with HTLV-II seropositivity (OR, 1.68; CI, 1.04-2.72). These data support a role for sexual transmission in HTLV-II infection. Association of seropositivity with primary residence in a traditional village (OR, 3.75; CI, 1.02-15.38) and lack of formal education (0 vs. >6 years [OR, 3.89; CI, 1.67-9.82]) observed in males may reflect differences in sexual practices associated with acculturation. (+info)
Haptoglobin 1F allele frequency is high among indigenous populations in the state of Durango, Mexico.
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We studied haptoglobin polymorphism in Mexican populations with high Indian ancestry living in isolated and urban areas in the state of Durango. Analysis with respect to the HP*1F and HP*1S allelic subtypes by isoelectric focusing showed unusually high HP*1F allele frequencies among urban (0.370) and isolated Mexican Indians (0.383). Comparison with other population studies demonstrated a geographical cline of the HP*1F allele increasing in the same direction of the HP*1 allele, while HP*1S frequency does not show racial differences. (+info)
Characterization of the lipid-binding properties and lipoprotein lipase inhibition of a novel apolipoprotein C-III variant Ala23Thr.
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We have identified a G-to-A transition in exon 3 of the APOC3 gene resulting in a novel Ala23Thr apolipoprotein (apo) C-III variant, associated with apoC-III deficiency in three unrelated Yucatan Indians. The Ala23Thr substitution modifies the hydrophobic/hydrophilic repartition of the helical N-terminal peptide and hence could disturb the lipid association. In vitro expression in Escherichia coli of wild-type and mutant apoC-III enabled the characterization of the variant. Compared with wild-type apoC-III-Ala23, the mutant apoC-III-Thr23 showed reduced affinity for dimyristoylphosphatidylcholine (DMPC) multilamellar vesicles with higher amounts of free apoC-III. Displacement of apoE from discoidal apoE:dipalmitoylphosphatidycholine (DPPC) complex by apoC-III-Thr23 was comparable to wild type but the less efficient binding of the apoC-III-Thr23 to the discoidal complex resulted in a higher apoE/apoC-III (mol/mol) ratio (34%) than with wild-type/apoE:DPPC mixtures. The inhibition of lipoprotein lipase (LPL) by apoC-III-Thr23 was comparable to that of wild type, and therefore effects on LPL activity could not explain the lower triglyceride (Tg) levels in Thr-23 carriers. Thus, these in vitro results suggest that in vivo the less efficient lipid binding of apoC-III-Thr23 might lead to a faster catabolism of free apoC-III, reflected in the reduced plasma apoC-III levels identified in Thr-23 carriers, and poorer competition with apoE, which might enhance clearance of Tg-rich lipoproteins and lower plasma Tg levels seen in Thr-23 carriers. (+info)
The dual origin and Siberian affinities of Native American Y chromosomes.
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The Y chromosomes of 549 individuals from Siberia and the Americas were analyzed for 12 biallelic markers, which defined 15 haplogroups. The addition of four microsatellite markers increased the number of haplotypes to 111. The major Native American founding lineage, haplogroup M3, accounted for 66% of male Y chromosomes and was defined by the biallelic markers M89, M9, M45, and M3. The founder haplotype also harbored the microsatellite alleles DYS19 (10 repeats), DYS388 (11 repeats), DYS390 (11 repeats), and DYS391 (10 repeats). In Siberia, the M3 haplogroup was confined to the Chukotka peninsula, adjacent to Alaska. The second major group of Native American Y chromosomes, haplogroup M45, accounted for about one-quarter of male lineages. M45 was subdivided by the biallelic marker M173 and by the four microsatellite loci alleles into two major subdivisions: M45a, which is found throughout the Americas, and M45b, which incorporates the M173 variant and is concentrated in North and Central America. In Siberia, M45a haplotypes, including the direct ancestor of haplogroup M3, are concentrated in Middle Siberia, whereas M45b haplotypes are found in the Lower Amur River and Sea of Okhotsk regions of eastern Siberia. Among the remaining 5% of Native American Y chromosomes is haplogroup RPS4Y-T, found in North America. In Siberia, this haplogroup, along with haplogroup M45b, is concentrated in the Lower Amur River/Sea of Okhotsk region. These data suggest that Native American male lineages were derived from two major Siberian migrations. The first migration originated in southern Middle Siberia with the founding haplotype M45a (10-11-11-10). In Beringia, this gave rise to the predominant Native American lineage, M3 (10-11-11-10), which crossed into the New World. A later migration came from the Lower Amur/Sea of Okhkotsk region, bringing haplogroup RPS4Y-T and subhaplogroup M45b, with its associated M173 variant. This migration event contributed to the modern genetic pool of the Na-Dene and Amerinds of North and Central America. (+info)
Molecular variability in Amerindians: widespread but uneven information.
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A review was made in relation to the molecular variability present in North, Central, and South American Indian populations. It involved results from ancient DNA, mitochondrial DNA in extant populations, HLA and other autosomal markers, X and Y chromosome variation, as well as data from parasitic viruses which could show coevolutionary changes. The questions considered were their origin, ways in which the early colonization of the continent took place, types and levels of the variability which developed, peculiarities of the Amerindian evolutionary processes, and eventual genetic heterogeneity which evolved in different geographical areas. Although much information is already available, it is highly heterogeneous in relation to populations and types of genetic systems investigated. Unfortunately, the present trend of favoring essentially applied research suggest that the situation will not basically improve in the future. (+info)
Differences in idiopathic inflammatory myopathy phenotypes and genotypes between Mesoamerican Mestizos and North American Caucasians: ethnogeographic influences in the genetics and clinical expression of myositis.
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OBJECTIVE: As part of a larger, worldwide study of the ethnogeography of myositis, we evaluated the clinical, serologic, and immunogenetic features of Mestizo (Mexican and Guatemalan) and North American Caucasian patients with idiopathic inflammatory myopathy (IIM). METHODS: Clinical manifestations, autoantibodies, HLA-DRB1 and DQA1 alleles, and immunoglobulin Gm/Km allotypes were compared between 138 Mestizos with IIM and 287 Caucasians with IIM, using the same classification criteria and standardized questionnaires. RESULTS: IIM in Mestizo patients was characterized by a higher proportion of dermatomyositis (69% of adult Mestizos versus 35% of adult Caucasians; P < 0.001) and anti-Mi-2 autoantibodies (30% versus 7% of adults, respectively, and 32% versus 4% of children, respectively; P < 0.01). Genetic risk factors also differed in these populations. Whereas Mestizos had no HLA risk factors for IIM, HLA-DRB1*0301, the linked allele DQA1*0501, and DRB1 alleles sharing the first hypervariable region motif (9)EYSTS(13) were major risk factors in Caucasian patients with IIM. Furthermore, different HLA-DRB1 and DQA1 alleles were associated with anti-Mi-2 autoantibodies (DRB1*04 and DQA1*03 in Mestizos and DRB1*07 and DQA1*02 in Caucasians). Immunoglobulin gamma-chain allotypes Gm(1), Gm(17) (odds ratio for both 11.3, P = 0.008), and Gm(21) (odds ratio 7.3, P = 0.005) and kappa-chain allotype Km(3) (odds ratio 7.3, P = 0.005) were risk factors for IIM in Mestizos; however, no Gm or Km allotypes were risk or protective factors in Caucasians. In addition, Gm and Km phenotypes were unique risk factors (Gm 1,3,17 5,13,21 and Gm 1,17 23 21 and Km 3,3) or protective factors (Km 1,1) for the development of myositis and anti-Mi-2 autoantibodies (Gm 1,2,3,17 23 5,13,21) in adult Mestizos. CONCLUSION: IIM in Mesoamerican Mestizos differs from IIM in North American Caucasians in the frequency of phenotypic features and in the immune-response genes predisposing to and protecting from myositis and anti-Mi-2 autoantibodies at 4 chromosomal loci. These and other data suggest the likelihood that the expression of IIM is modulated by different genes and environmental exposures around the world. (+info)