A functional ABCA1 gene variant is associated with low HDL-cholesterol levels and shows evidence of positive selection in Native Americans.

It has been suggested that the higher susceptibility of Hispanics to metabolic disease is related to their Native American heritage. A frequent cholesterol transporter ABCA1 (ATP-binding cassette transporter A1) gene variant (R230C, rs9282541) apparently exclusive to Native American individuals was associated with low high-density lipoprotein cholesterol (HDL-C) levels, obesity and type 2 diabetes in Mexican Mestizos. We performed a more extensive analysis of this variant in 4405 Native Americans and 863 individuals from other ethnic groups to investigate genetic evidence of positive selection, to assess its functional effect in vitro and to explore associations with HDL-C levels and other metabolic traits. The C230 allele was found in 29 of 36 Native American groups, but not in European, Asian or African individuals. C230 was observed on a single haplotype, and C230-bearing chromosomes showed longer relative haplotype extension compared with other haplotypes in the Americas. Additionally, single-nucleotide polymorphism data from the Human Genome Diversity Panel Native American populations were enriched in significant integrated haplotype score values in the region upstream of the ABCA1 gene. Cells expressing the C230 allele showed a 27% cholesterol efflux reduction (P< 0.001), confirming this variant has a functional effect in vitro. Moreover, the C230 allele was associated with lower HDL-C levels (P = 1.77 x 10(-11)) and with higher body mass index (P = 0.0001) in the combined analysis of Native American populations. This is the first report of a common functional variant exclusive to Native American and descent populations, which is a major determinant of HDL-C levels and may have contributed to the adaptive evolution of Native American populations.

Serum total homocysteine levels and the prevalence of folic acid deficiency and C677T mutation at the MTHFR gene in an indigenous population of Amazonia: the relationship of homocysteine with other cardiovascular risk factors.

Hyperhomocysteinemia is a risk factor for cardiovascular disease. C677T mutation at the MTHFR gene and deficiencies of folic acid and vitamin B-12 may account for elevation of total homocysteine (tHcy). Ninety Brazilian Parkatêjê Indians (90.0% of the population without admixture, aged > or = 20 years) were studied. Hyperhomocysteinemia was observed in 26.7% of the Indians. No case of vitamin B-12 deficiency was detected. Folic acid deficiency was found in 43.3% of the subjects. Rates of mutated allele 677T and TT genotype were 40.7% and 14.0%, respectively. Prevalence of hypertension, dyslipidemia, smoking, WHR > or = 0.9, BMI > or = 25 kg/m2 and chronic alcohol use were 4.4%, 44.4%, 25.6%, 72.2%, 67.8%, and 0.0%, respectively. All creatinine values were normal. Natural logarithmic (ln) tHcy showed no correlation with age, but was positively correlated with systolic (r = 0.22) and diastolic (r = 0.21) blood pressure and triglycerides (r = 0.39) and inversely correlated with folic acid (r = -0.40) adjusted for age and sex. Total homocysteine (tHcy) was higher among TT genotype (P < .001). The multiple linear regression model, containing variables for sex, folic acid, TT genotype, and triglycerides, explained 50.0% of the variation of the ln tHcy. In summary, high rates of cardiovascular risk factors were discovered. C667T mutation and folic acid deficiency can explain, at least in part, the observed hyperhomocysteinemia.

Metabolic profile and cardiovascular risk patterns of an Indian tribe living in the Amazon Region of Brazil.

The Parkatêjê Indians, belonging to the Jê group and inhabiting the Mãe Maria Reservation in the southeast of the state of Pará in the Amazon Region of Brazil, have suffered rapid and intensive cultural changes in recent years. This survey was designed to characterize the metabolic profile and the frequency of cardiovascular risk factors in this community. Ninety subjects (90.0% of the adult population without admixture) were investigated. Anthropometric measurements were performed and the following clinical characteristics measured: glycemia, serum insulin and proinsulin (fasting and 2-hr post 75 g of glucose load), beta-cell function (%B) and insulin sensitivity (%S) estimated by HOMA, HbA1c, GAD65 antibody, serum lipids, uric acid, creatinine, leptin, and blood pressure. Information about alcohol use, smoking, and medical history was obtained through individual interviews. The prevalences were: overweight, 67.8%; obesity, 14.4%; central obesity, 72.2%; hypertension, 4.4%; dyslipidemia, 44.4%; hyperuricemia, 5.6%; GAD65 antibody positivity, 4.4%; smoking, 25.6%; chronic alcohol use, 0.0%. One case of impaired glucose tolerance (1.1%) and one case of impaired fasting glycemia (1.1%) were diagnosed during this study and one case of diabetes (1.1%) was diagnosed previously. The diabetic woman was excluded from the analyses involving HbA1c, glycemia, insulin, proinsulin, %B, and %S. All creatinine values were normal. Blood pressure did not correlate with age, anthropometric measurements, insulin, proinsulin, and natural logarithm (ln) transformed %S. After adjustment for age and sex, there were positive correlations between total cholesterol and body mass index (BMI; r = 0.24), triglycerides and BMI (r = 0.44), triglycerides and waist-to-hip ratio (WHR; r = 0.52), In leptin and BMI (r = 0.41), In leptin and WHR (r = 0.29), uric acid and systolic blood pressure (r = 0.34), uric acid and triglycerides (r = 0.22). Systolic (r = 0.04; r = 0.70) and diastolic (r = 0.14; p = 0.18) blood pressure did not correlate with BMI. Ln leptin had a weak positive correlation with 2-hr insulin (r = 0.14) adjusted for age, sex, and BMI. The multiple linear regression model containing the variables sex, BMI, and 2-hr insulin concentrations explained 77.2% of the variation of ln leptin. In conclusion, the high rates of cardiovascular risk factors found among these Indians point to there being a high-risk group to develop diabetes and cardiovascular diseases. To reduce this risk they need to receive preventive interventions.

Relação da homocisteinemia com a sensibilidade à insulina e com fatores de risco cardiovascular em um grupo indígena brasileiro / Relationship of homocysteinemia with the insulin sensitivity and cardiovascular risk factors in a brazilian indians group

A hiper-homocisteinemia é um fator de risco cardiovascular independente, Há controvérsias sobre uma possível relação entre a homocisteína e a resistência/sensibilidade à insulina. Para testar a relação entre a homocisteinemia e a sensibilidade à insulina, noventa índios Parkatêjê (90 por cento da população adulta, sem miscigenação) tiveram os níveis séricos de homocisteína total (HPLC) dosados. A sensibilidade à insulina (porcentagem S) foi calculada pelo HOMA. Uma índia diabética foi excluída das análises envolvendo glicemia, insulina, pró-insulina, HbAI c e porcentagem S. Hiper-homocisteinemia e hiperinsulinemia ao jejum foram encontradas em 26,7 por cento e 25,8 porc ento dos índios, respectivamente. O logaritmo natural (In) da homocisteína correlacionou-se positivamente com a pressão arterial sistólica (r= 0,22) e diastólica (r= 0,21), triglicérides (r= 0,39) e ácido úrico (r= 0,40), após ajuste para idade e sexo, mas não com a insulina, pró-insulina e In porcentagem S. O In da homocisteína foi semelhante em todos os quartis de porcentagem S e também entre os indivíduos com e sem hiperinsulinemia de jejum. A insulina, pró-insulina e In porcentage S foram semelhantes entre os indivíduos com e sem hiper-homocisteinemia. Observamos correlações entre variáveis relacionadas ao risco cardiovascular, mas não entre essas variáveis e a insulina ou o In porcentagem S. Este achado talvez seja peculiar deste grupo, Concluindo, as variações nas concentrações séricas da homocisteína não estão relacionadas à insulina, à pró-insulina e à porcentagem S entre os Parkatêjê.

Doença de Wilson: relato de quatro casos; estudo evolutivo de um paciente durante 33 anos / Wilson's disease: report of 4 cases; evolutional study of one patient for 33 years

A moléstia de Wilson é uma doença rara, com relativamente poucas comunicaçöes quanto aos aspectos evolutivos a longo prazo. O objetivo foi o de relatar quatro casos, ressaltando seus aspectos clínicos e laboratoriais polimórficos e o estudo evolutivo de um deles durante 33 anos, cujo tratamento (medicamentos: dimercaptopropanol, sulfureto de potássio e penicilamina: orientaçäo alimentar e geral), possibilitou a regressäo dos sintomas e sinais da doença