João Paulo Botelho Vieira-Filho

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.

Metabolic Profile and Cardiovascular Risk Patterns of an Indian Tribe Living in the Amazon Region of Brazil

AbstractThe 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), ß-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), ln leptin and BMI (r = 0.41), ln 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.

Allelic polymorphisms of human Fcγ receptor IIa and Fcγ receptor IIIb among distinct groups in Brazil

BACKGROUND: The FcγRIIA gene is expressed in two polymorphic forms, R131 and H131, which differ by the replacement of histidine by arginine at position 131. The FCGR3B (FcγRIIIB) gene exists in two allelic isoforms, known as FCGR3B1 (FcγRIIIB‐NA1) and FCGR3B2 (FcγRIIIB‐NA2), which differ in nucleotides 141, 147, 227, 277, and 349. An additional polymorphism is the SH antigen that is associated with the FCGR3B3 (FcγRIIIB‐SH) allele.

Gene frequencies of the HPA‐15 (Gov) platelet alloantigen system in Brazilians

Summary.  The HPA‐15 (Gov) alloantigen is a biallelic co‐dominant system on human platelets, and its allele HPA‐15a and HPA‐15b differ by an A→C single nucleotide polymorphism at nucleotide 2108 of the coding sequence resulting in a Tyr682Ser substitution in the mature CD109 glycoprotein.

Gene frequencies of the HNA‐4a and ‐5a neutrophil antigens in Brazilian persons and a new polymerase chain reaction‐restriction fragment length polymorphism method for HNA‐5a genotyping

BACKGROUND: The HNA‐4a (Mart) and HNA‐5a (Ond) antigens are polymorphic variants of αM (CD11b) and αL (CD11a) subunits of the β2‐integrin, and are associated with single nucleotide polymorphisms (SNP) leading to amino acid dimorphisms. HNA‐4a has been linked to alloimmune neonatal neutropenia, but the HNA‐5a clinical significance is unclear.

HNA-3 gene frequencies in Brazilians and a new polymerase chain reaction-restriction fragment length polymorphism method for HNA-3a/3b genotyping

HNA‐3 antigens are the result of a rs2288904 single‐nucleotide polymorphism (SNP) in the CTL2, and the HNA‐3a and HNA‐3b variants are encoded by a guanine and adenine at Nucleotide Position 461. Anti‐HNA‐3 are involved in severe transfusion‐related acute lung injury reactions and in neonatal alloimmune neutropenia. Since the distribution of the HNA‐3 system was unknown in South Americans, in this study we determined the frequency of the HNA‐3 alleles in Brazilians.

Performance of glycated haemoglobin (HbA1c) as a screening test for diabetes and impaired glucose tolerance (IGT) in a high risk population—The Brazilian Xavante Indians

AIMS To examine the properties of HbA1c to detect diabetes and IGT in adult Brazilian Xavante Indians, a high risk population for diabetes. METHODS The survey was carried out between October 2010 and January 2012 and based on a 75 g oral glucose tolerance test (OGTT). Basal and 2h capillary glycaemia were measured by HemoCue Glucose 201+; HbA1c using an automated high-performance liquid chromatography analyzer (Tosoh G7). RESULTS 630 individuals aged ≥ 20 years were examined and 80 had a previous diagnosis of diabetes. Sensitivity, specificity and accuracy for HbA1c ≥ 6.5% (≥ 48 mmol/mol) were 71.3%, 90.5% and 87.2%. The areas under the ROC curve (AUC) was 0.88 (95%CI: 0.83-0.93). To identify IGT, HbA1c values between 5.7% and 6.4% (39-47 mmol/mol) presented sensitivity, specificity and accuracy of 87.2%, 24.7% and 51.4%, with an AUC of 0.62 (95%CI: 0.57-0.67). CONCLUSIONS The ADA/WHO proposed cut-off of 6.5% (48 mmol/mol) for HbA1c was adequate to detect diabetes among the Xavante. However, the performance of the ADA proposed cut-off points for pre-diabetes, when used to detect IGT was inadequate and should not be recommended.

Relação da homocisteinemia com a sensibilidade à insulina e com fatores de risco cardiovascular em um grupo indígena brasileiro

ABSTRACT Relationship of Homocysteine, Insulin Sensitivity and Cardiovascular RiskFactors among the Brazilian Parkateje Indians.Hyperhomocysteinemia is an independent cardiovascular risk factor. Thereare controversies about a possible relation between homocysteine andinsulin resistance/sensitivity. To test the relation between homocysteinemiaand insulin sensitivity, serum total homocysteine concentrations (HPLC) weremeasured in samples from ninety Parkateje Indians (90% of the adult popu-lation, without admixture). Insulin sensitivity (%S) was estimated by HOMA. Adiabetic woman was excluded from the analysis involving glycaemia,insulin, proinsulin, HbA1c and %S. Hyperhomocysteinemia and fasting hyper-insulinemia were found in 26.7% and 25.8% of Indians, respectively. Log-trans-formed (ln) homocysteine was positively correlated with systolic (r= 0.22) anddiastolic (r= 0.21) blood pressure, triglycerides (r= 0.39) and uric acid (r= 0.40),after adjustment for age and sex, but not with insulin, proinsulin and ln %S. Lnhomocysteine was similar among the quartiles of %S and between the sub-jects with and without fasting hyperinsulinemia. Insulin, proinsulin and ln %Swere similar between the subjects with and without hyperhomocisteinemia.Correlations between variables related to cardiovascular risk wereobserved, but not between these variables and insulin or ln %S. Perhaps thisfinding could be a peculiar characteristic of this group. In conclusion, the

Amyotrophic lateral sclerosis in a Brazilian Kayapó-Xikrin native

Dr. Clecio Godeiro-Junior – Rua Dr Diogo de Faria 650 / 33 04037-002 Sao Paulo SP Brasil. E-mail: cleciojunior@yahoo.com.br Amyotrophic lateral sclerosis (ALS) is one of the major neurodegenerative disorders alongside Alzheimer’s disease and Parkinson’s disease. It is a progressive disorder that involves degeneration of motor system at all levels, leading to muscle weakness and fatal course. Physical signs of this disease thus encompass both upper and lower motor neurons.The former is characterized by brisk reflexes and signs of pyramidal release such as Babinski sign, and the latter by muscle atrophy and fasciculation. The diagnostic criteria for ALS were published elsewhere . The incidence of sporadic ALS is between 1.5–2/ 100000 per year, giving a prevalence of around 6/100000. Males are usually more affected than females (ratio 1.6:1). In Brazil, an attempt to put together a comprehensive database to assess ALS’s epidemiological aspects was performed. The incidence and prevalence were lower than in Europe and USA. Regarding the clinical characteristics the same clinical pattern as in European and North-American patients was found. Minor differences in Brazilian patients were found on their lower age at onset and a higher incidence of bulbar onset among women. Several causal and pathogenic hypotheses for ALS have been proposed over the years, ranging from genetic to environmental etiology. Approximately 5–10% patients with the diagnosis of ALS present a positive family history. Autosomal recessive and dominant pattern of inheritance were already described. Between 10–20% of autosomal-dominant patients have mutations in superoxide dismuatse (SOD1) gene on chromosome 21. Numerous other genetic mutations were reported: angiogenin (14q11.2), vascular endothelial growth factor (6p12), survival motor neuron (5q12.2–q13.3), neurofilament protein (22q12.2), and charged multivesicular body protein 2B (2p11.2). A host of environmental factors have been investigated as potential risk factors, ranging from heavy-metal toxic effects to occupational exposures. Current research are focusing largely on excitotoxicity and oxidative stress, even the cycad exposure has been revisited. Chomorros, a native population of Guam Island, were the first group in which a clear environmental toxin exposure was related to increased risk of ALS. In Brazil, there is no description of a native group with increased risk of ALS. Herein we describe the first report of ALS in a Brazilian native of the Xikrin group. This group of natives belongs to a larger group known as Kayapo from “Je” linguistic family. Their village extends along the Catete river, in eastern Amazonia, State of Para, north of Brazil. The Xikrin were almost extinct by 1968, reaching the number of only 98. However, in the last four decades, with an appropriate health support, their population has been increasing due to a great number of births and reduction in infantile mortality, reaching a total population of 947 natives (512 male and 435 female) in July 2007. Figure shows Xikrin village during a traditional ritual for old and young men.

Cardiovascular Risk in Xavante Indigenous Population

Background The prevalence of cardiovascular risk factors is little known in Brazilian indigenous populations. In the last two decades, important changes have occurred in the lifestyle and epidemiological profile of the Xavante people. Objective to assess the prevalence of cardiovascular risk factors in Xavante adults in São Marcos and Sangradouro/Volta Grande reserves, in the state of Mato Grosso, Brazil. Methods Cross-sectional study carried out with 925 Xavante people aged ≥ 20 years between 2008 and 2012. The following indicators were assessed: triglycerides (TG), total, LDL and HDL-cholesterol, Castelli index I and II, TG/HDL-cholesterol ratio, apo B / Apo A1 ratio, Framingham risk score, C-reactive protein, body mass index (BMI), waist circumference (WC), hypertriglyceridemic waist (HW), glycemia and blood pressure. Kolmogorov-Smirnov, Students t test and Chi-square test (χ2) were used for statistical analysis, and significance level was set at 5%. Results High prevalence of elevated cardiovascular risk was observed in men and women according to HDL-cholesterol (66.2% and 86.2%, respectively), TG (53.2% and 51.5%), TG/HDL-cholesterol ratio (60.0% and 49.1%), C-reactive protein (44.1% and 48.1%), BMI (81.3% and 81.7%), WC (59.1% and 96.2%), HW (38.0% and 50,6%) and glycemia (46.8% and 70.2%). Individuals aged 40 to 59 years had the highest cardiovascular risk. Conclusions The Xavante have a high cardiovascular risk according to several indicators evaluated. The present analysis of cardiovascular risk factors provides support for the development of preventive measures and early treatment, in attempt to minimize the impact of cardiovascular diseases on this population.