Aguinaldo Luiz Simões

Prognostic factors and survival analysis in a sample of oral squamous cell carcinoma patients.

OBJECTIVES The aims of this report were to describe the 5-year overall survival (OS) in a group of oral squamous cell carcinoma (OSCC) patients and to investigate the effects of age, gender, anatomic localization, tumor evolution time, smoking and alcohol intake, nodal status, tumoral recurrences, histologic classification, p53 and p63 immunoexpression, human papillomavirus DNA presence, and treatment on the prognostic outcome. STUDY DESIGN Survival curves were generated using Kaplan-Meier method, and univariate and multivariate analyses were made using the log rank test and Cox regression, respectively. RESULTS The 5-year OS was 28.6%, and the univariate analysis showed significant results for p53 and p63 immunoexpression, age, and anatomic localization. The Cox regression demonstrated poor OS for tumors with p53 immunoexpression and for patients aged over 60 years. There were also significant differences in survival depending on the anatomic localizations. CONCLUSION These results highlight the influence of p53 immunoexpression, age, and anatomic localization in OSCC evolution.

HLA-G polymorphisms in women with squamous intraepithelial lesions harboring human papillomavirus

Human papillomavirus (HPV) infection is etiologically associated with low- (LSIL) and high-grade squamous intraepithelial lesions (HSIL) and with cervical cancer. The progression or regression of the lesions may depend, among other factors, on the host heritable immune response. Because human leukocyte antigen (HLA)-G molecules are involved in the modulation of innate and adaptive immune responses, and because no previous studies have evaluated HLA-G polymorphism in patients with SIL, we conducted a study to assess the association between HLA-G polymorphisms and cervical lesions harboring HPV infection. Cervico-vaginal scrapings and blood samples were collected from 125 women with SIL (68 LSIL and 57 HSIL) and from 94 healthy women without HPV infection and cytological abnormalities. HPV type and HLA-G polymorphisms in exons 2, 3 and 8 (14 bp insertion/deletion) were evaluated by PCR methodology, and digested with restriction endonucleases. The Genepop software and the EM and PHASE algorithms were used for statistical analysis. A significant protective association was observed between the presence of the G*0103 allele and SIL and between the G0101/G0104 genotype and HSIL in the group of patients compared to control. The presence of the G0104/+14 bp and G0104/−14 bp haplotypes conferred susceptibility to SIL compared to control. In addition, patients possessing the G0104/+14 bp haplotype and harboring HPV-16 and -18 co-infections were particularly associated with HSIL. These findings suggest that HLA-G polymorphisms may be associated with HPV infection and SIL, consequently representing a profile of predisposition to cervical cancer.

Endothelial nitric oxide synthase polymorphisms and haplotypes in Amerindians.

Interethnic disparities in the distribution of endothelial nitric oxide synthase (eNOS) polymorphisms may affect nitric oxide (NO)-mediated effects of and responses to drugs. While there are differences between black and white subjects there is no information regarding the distribution of eNOS gene alleles and haplotypes in Amerindians. We studied three clinically relevant eNOS polymorphisms (T(-786)C in the promoter, a variable number of tandem repeats in intron 4, and the Glu298Asp in exon 7) and eNOS haplotypes in 170 Amerindians from three tribes of the Brazilian Amazon. The results were compared with previous findings for black and white Brazilians. The Asp298, C(-786), and 4a alleles were much less common in Amerindians (5.0%, 3.2%, and 4.1%, respectively) than in blacks (15.1%, 19.5%, and 32.0%, respectively) or whites (32.8%, 41.9%, and 17.9%, respectively) (p < 0.001). The haplotype including the most common alleles for each polymorphism was much more common in Amerindians (89%) than in blacks (45%) or whites (41%). Our findings are consistent with a lower genetic diversity in Amerindians compared with blacks and whites. These striking differences may be of major relevance for case-control association studies focusing on eNOS gene polymorphisms and may explain, at least in part, differences in the responses to cardiovascular drugs.

Absence of the Δccr5 mutation in indigenous populations of the Brazilian Amazon

Abstract. Carriers of the Δccr5 allele, which contains a deletion of 32 bases in relation to the normal allele of the β-chemokine receptor gene (CCR5), have increased resistance to HIV-1 infection. The higher frequency of this mutation in Europeans than in Blacks and Asians, has generated interest in determining its distribution in other populations. The population of this study involved 300 Amerindians from four Brazilian Amazon tribes (Tikuna, Baniwa, Kashinawa, and Kanamari). All of the individuals were homozygous for the normal allele, which corroborates the hypothesis that the Δccr5 allele has a European origin, and that its occurrence in urban populations in South America is the result of immigration.

Genomic ancestry in urban Afro-Brazilians

Brazil is the result of interethnic crosses of European, African and Amerindian populations. Allelic frequencies for seven STR loci (TH01, TPOx, CSF1PO, vWA, FES/FPS, F13A1 and CD4), obtained from a sample of 70 individuals identified as Afro-Brazilian and 150 as mulatto, are presented here. Based on the frequencies of these genetic markers, estimates of interethnic admixture showed 62%, 26% and 12% of European, African and Amerindian contribution, respectively, for the mulatto sample and 37% and 63% of European and African contribution, respectively, for the Afro-Brazilian sample.

TNF Microsatellite Alleles in Brazilian Chagasic Patients

To evaluate the tumor necrosis factor (TNF) a–e microsatellite polymorphism in Chagasic patients, we studied 162 patients stratified according to the major clinical variants (cardiac, digestive, digestive plus cardiac, and indeterminate forms) and 221 healthy controls. TNF microsatellite alleles were typed using genomic DNA amplified with specific primers. Statistical analyses were performed using the GENEPOP and ARLEQUIN softwares and the two-tailed Fisher exact test. The TNFa2, TNFa7, TNFa8, TNFb2, TNFb4, TNFd5, TNFd7, and TNFe2 alleles were overrepresented, whereas the TNFb7 and TNFd3 alleles were underrepresented when clinical variants of Chagas’ disease or the patient group as a whole were compared with controls. Twelve TNF haplotypes were associated with susceptibility to or protection against Chagas’ disease, considered as a whole or stratified into clinical variants. Many of these haplotypes encompassed the above-described susceptibility/protective alleles. These results indicate that the TNF chromosomal region is relevant for Chagas’ disease development.

European Ancestry Predominates in Neuromyelitis Optica and Multiple Sclerosis Patients from Brazil

Background Neuromyelitis optica (NMO) is considered relatively more common in non-Whites, whereas multiple sclerosis (MS) presents a high prevalence rate, particularly in Whites from Western countries populations. However, no study has used ancestry informative markers (AIMs) to estimate the genetic ancestry contribution to NMO patients. Methods Twelve AIMs were selected based on the large allele frequency differences among European, African, and Amerindian populations, in order to investigate the genetic contribution of each ancestral group in 236 patients with MS and NMO, diagnosed using the McDonald and Wingerchuck criteria, respectively. All 128 MS patients were recruited at the Faculty of Medicine of Ribeirão Preto (MS-RP), Southeastern Brazil, as well as 108 healthy bone marrow donors considered as healthy controls. A total of 108 NMO patients were recruited from five Neurology centers from different Brazilian regions, including Ribeirão Preto (NMO-RP). Principal Findings European ancestry contribution was higher in MS-RP than in NMO-RP (78.5% vs. 68.7%) patients. In contrast, African ancestry estimates were higher in NMO-RP than in MS-RP (20.5% vs. 12.5%) patients. Moreover, principal component analyses showed that groups of NMO patients from different Brazilian regions were clustered close to the European ancestral population. Conclusions Our findings demonstrate that European genetic contribution predominates in NMO and MS patients from Brazil.

Genetic diversity of the HLA-G coding region in Amerindian populations from the Brazilian Amazon: a possible role of natural selection

HLA-G has an important role in the modulation of the maternal immune system during pregnancy, and evidence that balancing selection acts in the promoter and 3′UTR regions has been previously reported. To determine whether selection acts on the HLA-G coding region in the Amazon Rainforest, exons 2, 3 and 4 were analyzed in a sample of 142 Amerindians from nine villages of five isolated tribes that inhabit the Central Amazon. Six previously described single-nucleotide polymorphisms (SNPs) were identified and the Expectation-Maximization (EM) and PHASE algorithms were used to computationally reconstruct SNP haplotypes (HLA-G alleles). A new HLA-G allele, which originated in Amerindian populations by a crossing-over event between two widespread HLA-G alleles, was identified in 18 individuals. Neutrality tests evidenced that natural selection has a complex part in the HLA-G coding region. Although balancing selection is the type of selection that shapes variability at a local level (Native American populations), we have also shown that purifying selection may occur on a worldwide scale. Moreover, the balancing selection does not seem to act on the coding region as strongly as it acts on the flanking regulatory regions, and such coding signature may actually reflect a hitchhiking effect.

Afro-derived Brazilian populations: male genetic constitution estimated by Y-chromosomes STRs and AluYAP element polymorphisms.

The genetic constitution of Afro‐derived Brazilian populations is barely studied. To improve that knowledge, we investigated the AluYAP element and five Y‐chromosome STRs (DYS19, DYS390, DYS391, DYS392, and DYS393) to estimate ethnic male contribution in the constitution of four Brazilian quilombos remnants: Mocambo, Rio das Rãs, Kalunga, and Riacho de Sacutiaba. Results indicated significant differences among communities, corroborating historical information about the Brazilian settlement. We concluded that besides African contribution, there was a great European participation in the constitution of these four populations and that observed haplotype variability could be explained by gene flow to quilombos remnants and mutational events in microsatellites (STRs). Am. J. Hum. Biol., 2009.

Demographic and blood genetic characteristics in an Amazonian population

Demographic, epidemiological and genetic studies are reported from 595 persons living in Parintins, a community situated at the extreme East of the State of Amazonas, Brazil. The average distance traveled by the adults studied from their birthplaces to Parintins was 116 kms. Marital distances, estimated in three generations, ranged from 35 km to 174 km, and parent-offspring distances from 88 km to 157 km. Most of these dispersion measures showed a high degree of correlation. The genetic data involved nine systems (ABO, Rh, Hb, ESD, CA 2 , Hp, Tf, Cp and Al). One special item of interest was the occurrence of the rare variant ESD 4 . Largely negative results concerning specific phenotype differences in malaria susceptibility, as well as in general mortality or fertility, were obtained. Preliminary quantitative estimates of the racial composition of this trihybrid mixed population indicates that it should be 67% White, 29% Indian and 4% Black.