No abstract

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/ þ 14 bp and G0104/À14 bp haplotypes conferred susceptibility to SIL compared to control. In addition, patients possessing the G0104/ þ 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.

Allelic frequencies of eight autosomal short-tandem repeat (STR) loci (TH01, TPOx, CSF1PO, vWA, FES/FPS, F13A1, F13B, and CD4) were determined in 400 individuals born in the State of São Paulo. No significant deviations from Hardy-Weinberg equilibrium were found in any loci analyzed. The Unweighted Pair-Group Method with Arithmetic Mean (UPGMA) tree constructed based on genetic distances revealed that the present population was grouped with Europeans, and separated from African and Amerindian populations. Estimates of admixture components based on the gene identity method revealed 79% European, 14% African, and 7% Amerindian contributions to this Brazilian population sample.

Ancestry informative markers (AIMs) are genetic loci with large frequency differences between the major ethnic groups and are very useful in admixture estimation. However, their frequencies are poorly known within South American indigenous populations, making it difficult to use them in admixture studies with Latin American populations, such as the trihybrid Brazilian population. To minimize this problem, the frequencies of the AIMs FY-null, RB2300, LPL, AT3-I/D, Sb19.3, APO, and PV92 were determined via PCR and PCR-RFLP in four tribes from Brazilian Amazon (Tikúna, Kashinawa, Baníwa, and Kanamarí), to evaluate their potential for discriminating indigenous populations from Europeans and Africans, as well as discriminating each tribe from the others. Although capable of differentiating tribes, as evidenced by the exact test of population differentiation, a neighbor-joining tree suggests that the AIMs are useless in obtaining reliable reconstructions of the biological relationships and evolutionary history that characterize the villages and tribes studied. The mean allele frequencies from these AIMs were very similar to those observed for North American natives. They discriminated Amerindians from Africans, but not from Europeans. On the other hand, the neighbor-joining dendrogram separated Africans and Europeans from Amerindians with a high statistical support (bootstrap = 0.989). The relatively low diversity (G(ST) = 0.042) among North American natives and Amerindians from Brazilian Amazon agrees with the lack of intra-ethnic variation previously reported for these markers. Despite genetic drift effects, the mean allelic frequencies herein presented could be used as Amerindian parental frequencies in admixture estimates in urban Brazilian populations.

BackgroundNeuromyelitis 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.MethodsTwelve 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 FindingsEuropean 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.ConclusionsOur findings demonstrate that European genetic contribution predominates in NMO and MS patients from Brazil.

HLA-G (human leukocyte antigen-G) plays an important role in the modulation of the maternal immune system during pregnancy. HLA-G alleles presenting a 14-bp insertion at exon 8 have been associated with decreased messenger RNA levels, preeclampsia, and miscarriages. This suggests that natural selection may exert a strong influence against the insertion allele in isolated populations. DNA samples from 384 Amazonian Indians spread across seven isolated tribes were evaluated for the 14-bp polymorphism. The insertion frequency (38.54%) was somewhat low. The Ewens-Watterson's neutrality test showed a slight trend toward balancing selection operating at this locus but no correlation between the 14-bp locus and fertility data was found. To sum up, no definitive evidence was obtained indicating that the 14-bp frequencies in Amerindians depart from neutrality.

Data are presented on electrophoretic variants of 25 polypeptides found in the blood serum and erythrocytes, in 812 individuals from three Amerindian tribes, the Pano, the Baniwa, and the Kanamari. Two "private polymorphisms" were encountered, of PEPB in the Pano and CAII in the Baniwa. A single example of a different PEPB variant was encountered in the Baniwa, and two possible examples of an unstable variant of HGB A2 in the Kanamari. In addition, the well-known A variant of ACP1, the Duarte variant of GALT, the 2 variant of Hp and the 2 variant of PGM1 occurred in polymorphic proportions in all three tribes, and the TFDChi variant was present as a polymorphism in the Baniwa. These data have recently been incorporated into a treatment which concludes that the eight electrophoretically-defined "private polymorphisms" thus far encountered in Amerindian tribes can be explained by a mutation pressure of 0.7 x 10(-5)/locus/generation on the assumption of neutrality of the phenotypes in question (Neel and Thompson, '78).

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.