Introduction The nudix hydrolase 15 (NUDT15) gene acts in the metabolism of thiopurine, by catabolizing its active metabolite thioguanosine triphosphate into its inactivated form, thioguanosine monophosphate. The frequency of alternative NUDT15 alleles, in particular those that cause a drastic loss of gene function, varies widely among geographically distinct populations. In the general population of northern Brazilian, high toxicity rates (65%) have been recorded in patients treated with the standard protocol for acute lymphoblastic leukemia, which involves thiopurine-based drugs. The present study characterized the molecular profile of the coding region of the NUDT15 gene in two groups, non-admixed Amerindians and admixed individuals from the Amazon region of northern Brazil. Methods The entire NUDT15 gene was sequenced in 64 Amerindians from 12 Amazonian groups and 82 admixed individuals from northern Brazil. The DNA was extracted using phenol-chloroform. The exome libraries were prepared using the Nextera Rapid Capture Exome (Illumina) and SureSelect Human All Exon V6 (Agilent) kits. The allelic variants were annotated in the ViVa ® (Viewer of Variants) software. Results Four NUDT15 variants were identified: rs374594155, rs1272632214, rs147390019, andrs116855232. The variants rs1272632214 and rs116855232 were in complete linkage disequilibrium, and were assigned to the NUDT15*2 genotype. These variants had high

The manifestation of the COVID-19 varies from absence of symptoms to Severe Acute Respiratory Syndrome. The epidemiological data indicate that infection and mortality rates are greater in European populations in comparison with eastern Asians. To test if epidemiological patterns may be partly determined by human genetic variation, we investigated, by exomic and databank analyses, the variability found in the TMPRSS2 gene in populations from different continents, since this gene is fundamental to virus access into human cells. The functional variants revealed low diversity. The analyses of the variation in the modifiers of gene expression indicate that the European populations may have much higher levels of pulmonary expression of the TMPRSS2 gene and would be more vulnerable to infection by SARS-CoV-2. By contrast, the pulmonary expression of the TMPRSS2 may be reduced in the populations from East Asia, which implies that they are less susceptible to the virus infection and, these genetic features might also favor their better outcomes. The presented data, if confirmed, indicates a potential genetic contribution of TMPRSS2 to individual susceptibility to viral infection, and might also influence COVID-19 outcome.

In recent years, the incidence of tuberculosis (TB) has declined worldwide, although this disease still occurs at relatively high rates in Amerindian populations. This suggests that the genetic ancestry of Amerindians may be an important factor in the development of infections, and may account for at least some of the variation in infection rates in the different populations. The present study investigated the potential influence of Amerindian genetic ancestry on susceptibility to tuberculosis in an Amazon population. The study included 280 patients diagnosed with tuberculosis and 138 asymptomatic hospital employees with no history of TB, but who were in contact with bacterially active TB patients. Ancestry analysis was run on a set of 61 Ancestry-Informative Markers to estimate European, African, and Amerindian genetic ancestry using STRUCTURE v2.2. The TB group had significantly higher Amerindian ancestry in comparison with the control group, and significantly lower European ancestry. Amerindian ancestry in the 20-60% range was found to be the principal risk factor for increased susceptibility to TB. The results of the study indicate that Amerindian ancestry is an important risk factor for susceptibility to TB in the admixed population of the Brazilian Amazon region.

Objectives: Tuberculosis (TB) is an infectious and contagious disease that has been very influential in human history and presents high rates of mortality. The objective of this study was to investigate the association of VDR, IL10, and SLC11A1 gene polymorphisms with susceptibility to the presence of Mycobacterium tuberculosis infection. Methods: A total of 135 patients with confirmed TB and 141 healthy individuals were included in the analysis. Blood samples were collected for DNA extraction. Genotyping of the polymorphisms in the VDR and IL10 genes was performed by real-time PCR, and genotyping of the polymorphisms in the SLC11A1 gene by conventional PCR, followed by visualization in polyacrylamide gel. The genomic ancestry was obtained using an autosomal panel with 48 insertion/deletion ancestry-informative markers. Results: Polymorphisms TaqI (TT, p = 0.004), FokI (CC and CC + CT, p = 0.012 and p = 0.003, respectively), and BsmI (GG, p = 0.008) in the VDR gene, as well as A-592C (GC + AG, p = 0.001) in the IL10 gene, were significantly associated with susceptibility to TB In addition, high production of VDR combined with low production of IL10 showed protection for the TB group (p = 0.035). Conclusions: The VDR polymorphisms may confer an increased risk and the IL10 haplotype may be a protection factor for the presence of M. tuberculosis infection in the Brazilian population.

Prostate cancer (PCa) incidence and mortality vary across territories and populations. This can be explained by the genetic factor of this disease. This article aims to correlate the epidemiological data, worldwide incidence, and mortality of PCa with single-nucleotide polymorphisms (SNPs) associated with the susceptibility and severity of this neoplasm in different populations. Eighty-four genetic variants associated with prostate cancer susceptibility were selected from the literature through genome association studies (GWAS). Allele frequencies were obtained from the 1000 Genomes Project, and epidemiological data were obtained from Surveillance, Epidemiology, and End Results (SEER). The PCa incidence, mortality rates, and allele frequencies of variants were evaluated by Pearson’s correlation. Our study demonstrated that 12 SNPs (rs2961144, rs1048169, rs7000448, rs4430796, rs2066827, rs12500426, rs6983267, rs11649743, rs2075110, rs114798100, rs855723, and rs2075109) were correlated with epidemiological data in different ethnic groups. Ten SNPs (rs2961144, rs1048169, rs7000448, rs4430796, rs2066827, rs12500426, rs11649743, rs2075110, rs114798100, and rs2075109) were positively correlated with the mortality rate. Seven SNPs (rs1048169, rs2961144, rs7000448, rs4430796, rs2066827, rs12500426, and rs114798100) were positively correlated with incidence. Positive correlations of incidence and mortality rates were more frequent in the African population. The genetic variants investigated here are likely to predispose to PCa and could play a role in its progression and aggressiveness. This genetic study demonstrated here is promising for implementing personalized strategies to screen for prostate cancer in diverse populations.