TY - JOUR T1 - DEFB1 gene polymorphisms and tuberculosis in a Northeastern Brazilian population. JF - Braz J Microbiol Y1 - 2016 A1 - Celerino da Silva, Ronaldo A1 - da Cruz, Heidi Lacerda Alves A1 - Brandão, Lucas André Cavalcanti A1 - Guimarães, Rafael Lima A1 - Montenegro, Lilian Maria Lapa A1 - Schindler, Haiana Charifker A1 - Segat, Ludovica A1 - Crovella, Sergio AB -

β-Defensin-1, an antimicrobial peptide encoded by the DEFB1 gene, is known to play an important role in lung mucosal immunity. In our association study we analyzed three DEFB1 functional polymorphisms -52G>A (rs1799946), -44C>G (rs1800972) and -20G>A (rs11362) in 92 tuberculosis patients and 286 healthy controls, both from Northeast Brazil: no association was found between the studied DEFB1 polymorphisms and the disease. However we cannot exclude that this lack of association could be due to the low number of subjects analyzed, as suggested by the low statistical power achieved for the three analyzed SNPs (values between 0.16 and 0.50).

VL - 47 IS - 2 U1 - http://www.ncbi.nlm.nih.gov/pubmed/26991287?dopt=Abstract ER - TY - JOUR T1 - TRIM5 gene polymorphisms in HIV-1-infected patients and healthy controls from Northeastern Brazil. JF - Immunol Res Y1 - 2016 A1 - Celerino da Silva, Ronaldo A1 - Coelho, Antônio Victor Campos A1 - Arraes, Luiz Claudio A1 - Brandão, Lucas André Cavalcanti A1 - Crovella, Sergio A1 - Guimarães, Rafael Lima AB -

Humans show heterogeneity in vulnerability to HIV-1 infection, partially under control of genes involved in host immunity and virus replication. TRIM5α protein has restriction activity against replication of many retroviruses. Human TRIM5 gene single nucleotide polymorphisms have been reported as involved in susceptibility to HIV-1 infection. We recruited 213 HIV-1-positive patients and 234 healthy uninfected controls from Northeast Brazil; two non-synonymous variants at exon 2, rs3740996 (H43Y) and rs10838525 (R136Q), and one regulatory polymorphism (rs16934386) at 5'UTR region of TRIM5 were analyzed. The R136Q variation presented significant differences between HIV-1-positive patients and healthy controls. The 136Q allele and the 136QQ genotype were more frequent in healthy controls (32.7 and 10.2 %, respectively) than in HIV-1-positive patients (136Q allele: 24.4 %; OR 0.66; CI 95 % 0.49-0.90; p value = 0.008/136QQ genotype: 4.2 %; OR 0.33; CI 95 % 0.13-0.79, p = 0.008) also after adjusting for age and sex. We also stratified our findings according to the presence of CCR5Δ32 variation, but the results remained the same. We observed that rs10838525 (R136Q) and rs3740996 (H43Y) were in linkage disequilibrium (D' = 0.71), forming four possible haplotypes. The H43-136Q haplotype was significantly more frequent in healthy controls (28.2 %) than in HIV-positive patients (21.4 %; OR 0.69; CI 95 % 0.50-0.96; p = 0.022). An increased frequency of allele (136Q) and genotype (136QQ) of the non-synonymous rs10838525 (R136Q) variant and the haplotype (43H-136Q) was observed among healthy controls individuals. Being aware of the limitation of this study (unavailability of exposed but uninfected individuals), we hypothesize a potential role for TRIM5 variations in the protection against HIV-1 infection.

U1 - http://www.ncbi.nlm.nih.gov/pubmed/27388872?dopt=Abstract ER - TY - JOUR T1 - Meta-analysis and time series modeling allow a systematic review of primary HIV-1 drug-resistant prevalence in Latin America and Caribbean. JF - Curr HIV Res Y1 - 2015 A1 - Coelho, Antônio Victor Campos A1 - De Moura, Ronald Rodrigues A1 - da Silva, Ronaldo Celerino A1 - Kamada, Anselmo Jiro A1 - Guimarães, Rafael Lima A1 - Brandão, Lucas André Cavalcanti A1 - Coelho, Hemílio Fernandes Campos A1 - Crovella, Sergio AB -

Here we review the prevalence of HIV-1 primary drug resistance in Latin America and Caribbean using meta-analysis as well as time-series modeling. We also discuss whether there could be a drawback to HIV/AIDS programs due to drug resistance in Latin America and Caribbean in the next years. We observed that, although some studies report low or moderate primary drug resistance prevalence in Caribbean countries, this evidence needs to be updated. In other countries, such as Brazil and Argentina, the prevalence of drug resistance appears to be rising. Mutations conferring resistance against reverse transcriptase inhibitors were the most frequent in the analyzed populations (70% of all mutational events). HIV-1 subtype B was the most prevalent in Latin America and the Caribbean, although subtype C and B/F recombinants have significant contributions in Argentina and Brazil. Thus, we suggest that primary drug resistance in Latin America and the Caribbean could have been underestimated. Clinical monitoring should be improved to offer better therapy, reducing the risk for HIV-1 resistance emergence and spread, principally in vulnerable populations, such as men who have sex with men transmission group, sex workers and intravenous drug users.

VL - 13 IS - 2 U1 - http://www.ncbi.nlm.nih.gov/pubmed/25777517?dopt=Abstract ER - TY - JOUR T1 - Meta-analysis of Brazilian genetic admixture and comparison with other Latin America countries. JF - Am J Hum Biol Y1 - 2015 A1 - Moura, Ronald Rodrigues de A1 - Coelho, Antônio Victor Campos A1 - Balbino, Valdir de Queiroz A1 - Crovella, Sergio A1 - Brandão, Lucas André Cavalcanti AB -

OBJECTIVES: This study aims at performing a systematic review and meta-analysis with the studies of genetic admixture inference of Brazilian population and to compare these results with the genetic admixture levels in other Latin American countries.

METHODS: We searched for articles regarding the estimation of Brazilian genetic admixture published between 1980 and 2014 that used autosomal markers. Then, conducted meta-analyses at the whole-country and regional level. Finally, we compared the results of Brazil with other estimates from other South, Central and North American countries.

RESULTS: We analyzed data from 25 studies in 38 different Brazilian populations. European (EUR) ancestry is the major contributor to the genetic background of Brazilians, followed by African (AFR), and Amerindian (AMR) ancestries. The pooled ancestry contributions were 0.62 EUR, 0.21 AFR, and 0.17AMR. The Southern region had a greater EUR contribution (0.77) than other regions. Individuals from the Northeast (NE) region had the highest AFR contribution (0.27) whereas individuals from the North regions had more AMR contribution (0.32). In the Latin America context, Brazil has the 5th high EUR contribution, the 12th for the AFR component and the 10th for the AMR ancestry.

CONCLUSIONS: Admixture proportions vary greatly among Brazilian populations and also through Latin America. More studies in the Center-West, North and NE regions are needed to capture a more complete picture of the genomic ancestry of Brazil.

VL - 27 IS - 5 U1 - http://www.ncbi.nlm.nih.gov/pubmed/25820814?dopt=Abstract ER - TY - JOUR T1 - DC-SIGN polymorphisms are associated to type 1 diabetes mellitus. JF - Immunobiology Y1 - 2014 A1 - da Silva, Ronaldo Celerino A1 - Cunha Tavares, Nathália de Alencar A1 - Moura, Ronald A1 - Coelho, Antônio A1 - Guimarães, Rafael Lima A1 - Araújo, Jacqueline A1 - Crovella, Sergio A1 - Brandão, Lucas André Cavalcanti A1 - Silva, Jaqueline de Azevêdo KW - Adolescent KW - Alleles KW - Case-Control Studies KW - Cell Adhesion Molecules KW - Child KW - Child, Preschool KW - Diabetes Mellitus, Type 1 KW - Female KW - Gene Frequency KW - Genetic Association Studies KW - Genetic Predisposition to Disease KW - Genotype KW - Humans KW - Infant KW - Infant, Newborn KW - Lectins, C-Type KW - Male KW - Odds Ratio KW - Polymorphism, Genetic KW - Polymorphism, Single Nucleotide KW - Promoter Regions, Genetic KW - Receptors, Cell Surface AB -

Type I diabetes mellitus (T1DM) is an autoimmune disorder featured by raised glucoses levels. It has been hypothesised that raised glucose levels in T1DM might be recognised as PAMPs, leading to immune response by overloading the cell receptors for pathogens recognition. DC-SIGN is a transmembrane protein, present in dendritic cells (DC) and macrophages: it has an important role in inflammatory response and T cells activation. Notably, DC-SIGN activation and triggering of the immune response depend on the type of ligand, which may lead to a pro or anti-inflammatory pathway. In our association study, we analysed the SNPs rs4804803 (-336 A>G) and rs735239 (-871 A>G), both at DC-SIGN promoter region, in 210 T1DM patients and 157 healthy controls, also looking for a correlation with the age of onset of the disease. We found that the allele G and genotypes G/G and A/G of SNP-871 (rs735239), as well as the alleles G-G (rs735239-rs4804803) and genotypes combined AA-GG (rs735239-rs4804803) were associated with protection of T1DM development. We did not find association between these variations with the age of onset of the disease and the presence of other autoimmune disorders. Our results suggest that SNPs in DC-SIGN promoter region can be associated to protection for T1DM in the Northeast Brazilian population.

VL - 219 IS - 11 U1 - http://www.ncbi.nlm.nih.gov/pubmed/25092567?dopt=Abstract ER - TY - JOUR T1 - NLRP3 polymorphism is associated with protection against human T-lymphotropic virus 1 infection. JF - Mem Inst Oswaldo Cruz Y1 - 2014 A1 - Kamada, Anselmo Jiro A1 - Pontillo, Alessandra A1 - Guimarães, Rafael Lima A1 - Loureiro, Paula A1 - Crovella, Sergio A1 - Brandão, Lucas André Cavalcanti KW - Adult KW - Brazil KW - Carrier Proteins KW - Female KW - Genetic Predisposition to Disease KW - HTLV-I Infections KW - Human T-lymphotropic virus 1 KW - Humans KW - Inflammasomes KW - Interleukin-1 KW - Male KW - Middle Aged KW - Polymorphism, Single Nucleotide KW - Protective Factors AB -

Inter-individual heterogeneity in the response to human T-lymphotropic virus 1 (HTLV-1) infection has been partially attributed to host genetic background. The antiviral activity of the inflammasome cytoplasmic complex recognises viral molecular patterns and regulates immune responses via the activation of interleukin (IL)-1 family (IL-1, IL-18 and IL-33) members. The association between polymorphisms in the inflammasome receptors NLRP1 and NLRP3 and HTLV-1 infection was evaluated in a northeastern Brazilian population (84 HTLV-1 carriers and 155 healthy controls). NLRP3 rs10754558 G/G was associated with protection against HTLV-1 infection (p = 0.012; odds ratio = 0.37). rs10754558 affects NLRP3 mRNA stability; therefore, our results suggest that higher NLRP3 expression may augment first-line defences, leading to the effective protection against HTLV-1 infection.

VL - 109 IS - 7 U1 - http://www.ncbi.nlm.nih.gov/pubmed/25411003?dopt=Abstract ER - TY - JOUR T1 - Frequency distribution of HLA DQ2 and DQ8 in celiac patients and first-degree relatives in Recife, northeastern Brazil. JF - Clinics (Sao Paulo) Y1 - 2011 A1 - Castro-Antunes, Margarida Maria A1 - Crovella, Sergio A1 - Brandão, Lucas André Cavalcanti A1 - Guimarães, Rafael Lima A1 - Motta, Maria Eugênia Farias Almeida A1 - Silva, Giselia Alves Pontes da KW - Adolescent KW - Adult KW - Brazil KW - Celiac Disease KW - Chi-Square Distribution KW - Child KW - Child, Preschool KW - Cross-Sectional Studies KW - Europe KW - Family KW - Female KW - Gene Frequency KW - Genetic Predisposition to Disease KW - HLA-DQ Antigens KW - Humans KW - Infant KW - Male KW - Middle Aged KW - Young Adult AB -

AIMS: The aim of this study was to evaluate the frequencies of the HLA genotypes DQ2 and DQ8 and the alleles A1*05, A1*0201, B1*0201 and B1*0302 in individuals with celiac disease in Recife, northeastern Brazil.

METHODS: HLA DQ2 and DQ8 genotyping was performed for 73 individuals with celiac disease and 126 first-degree relatives with negative transglutaminase serology. The alleles DQA1*05, DQA1*0201, DQB1*02 and DQB1*0302 were identified by sequencing using specific primers and the EU-DQ kit from the Eurospital Laboratory, Trieste, Italy and double-checked by the All Set SPP kit (Dynal).

RESULTS: Among the 73 cases, 50 (68.5%) had the genotype DQ2, 13 (17.8%) had DQ8, 5 (6.8%) had DQ2 and DQ8, and 5 did not have any of these genotypes. Among the 5 negative individuals, four had the B1*02 allele and one did not have any of the alleles studied. B1*02 was the most frequent allele in both groups (94% in the patients and 89% in the control relatives).

CONCLUSIONS: In this study, celiac disease was associated with the genotypes DQ2 and DQ8. DQ2 predominated, but the distribution of the frequencies was different from what has been found in European populations and was closer to what has been found in the Americas. The high frequencies of the HLA genotypes DQ2 and DQ8 that were found in first-degree relatives would make it difficult to use these HLA genotypes for routine diagnosis of celiac disease in this group.

VL - 66 IS - 2 U1 - http://www.ncbi.nlm.nih.gov/pubmed/21484038?dopt=Abstract ER - TY - JOUR T1 - Mannose binding lectin gene (MBL2) functional polymorphisms are associated with systemic lupus erythematosus in southern Brazilians. JF - Hum Immunol Y1 - 2011 A1 - Sandrin-Garcia, Paula A1 - Brandão, Lucas André Cavalcanti A1 - Coelho, Antônio Victor Campos A1 - Guimarães, Rafael Lima A1 - Pancoto, João Alexandre Trés A1 - Segat, Ludovica A1 - Donadi, Eduardo Antônio A1 - de Lima-Filho, José Luiz A1 - Crovella, Sergio KW - Adolescent KW - Adult KW - Aged KW - Brazil KW - DNA Mutational Analysis KW - Female KW - Gene Frequency KW - Genetic Association Studies KW - Genetic Predisposition to Disease KW - Genotype KW - Humans KW - Lupus Erythematosus, Systemic KW - Male KW - Mannose-Binding Lectin KW - Middle Aged KW - Polymorphism, Genetic KW - Population Groups KW - Promoter Regions, Genetic AB -

Susceptibility to systemic lupus erythematosus (SLE) has been associated with immunologic, environmental, and genetic factors. To uncover a possible association between MBL2 gene polymorphisms and SLE, we analyzed functional polymorphisms in the promoter and first exon of the MBL2 gene in 134 Brazilian SLE patients and 101 healthy controls. Genotype and allele frequencies of MBL2 A/O polymorphism were significantly different between patients and controls, and the O allele was associated with an increased risk of SLE. An association between low mannose binding lectin (MBL) producer combined genotypes and increased risk for SLE was also reported. Furthermore, when stratifying SLE patients according to clinical and laboratory data, an association between the A/O genotype and nephritic disorders and between the X/Y genotype and antiphospholipid syndrome was evident. Combined genotypes responsible for low MBL production were more frequently observed in SLE patients with nephritis. Our results indicate MBL2 polymorphisms as possible risk factors for SLE development and disease-related clinical manifestations.

VL - 72 IS - 6 U1 - http://www.ncbi.nlm.nih.gov/pubmed/21510992?dopt=Abstract ER -