Northeastern Brazilian Population Research Articles

The association of A-1438G and T102C polymorphisms in HTR2A and 120 bp duplication in DRD4 with alcoholic dependence in a northeastern Brazilian male population

BackgroundAround the world, 3.3 million deaths are related to alcohol abuse. In Brazil, there are more than 4 million people with this behavior. Alcohol Dependence (AD) is a complex psychiatric disorder characterized by excessive alcohol consumption influenced by genetic and environmental factors. HTR2A and DRD4 are genes related to the serotonergic and dopaminergic systems and alterations in their sequences are associated with the etiology of AD. Our work analyzed the association between A-1438G (rs6311) and T102C (rs6313) polymorphisms in HTR2A and 120 bp duplication in DRD4 with the susceptibility to AD in that group of people. MethodsBlood samples were collected from 300 men from Northeastern Brazil (150 alcohol-dependents and 150 controls). After DNA extraction, the determination of HTR2A and DRD4 genotypes was performed through PCR-RFLP method. The allele and genotype frequencies and association of polymorphisms with AD were determined using chi-square and Fisher's exact test, as well as, odds ratio (OR) with confidence interval of 95%. Value of p < 0.05 was considered significant. ResultsSignificantly, the low education, intake of doses per day, smoking and a positive family background of alcoholics were predominant in alcoholics patients than controls (p < 0.05). The results showed no differences were found between polymorphisms in the HTR2A and DRD4 genes herein investigated with AD. However, we observed a significant association between the GG (GG: OR = 6.68; 95% CI: 2.85 to 15.68; p < 0.0001), CC (CC: OR = 4.34; 95% CI: 1.68 to 11.1; p = 0.003), AG + GG (AG + GG: OR = 5.96; 95% CI: 2.68 to 13.2; p = 0.0001) and, TC + CC (TC + CC: OR = 4.38; 95% CI: 1.79 to 10.6; p = 0.001) genotypes in the HRT2A gene and family background with susceptibility to AD in our population. ConclusionTherefore, we suggest that the homozygous and heterozygous genotypes of the A-1438G and T102C polymorphism in the HTR2A gene, together with the positive family AD history, may be associated with the development of AD in the northeastern Brazilian male population displaying a dominant inheritance model. Further work is strongly encouraged to confirm the role of these polymorphisms in AD.

IL1β, IL18, NFKB1 and IFNG gene interactions are associated with severity of rheumatoid arthritis: A pilot study

Rheumatoid arthritis (RA) is an autoimmune disease which can lead to progressive and functional disability. Literature data suggest that some inflammatory proteins are dysregulated in RA patients and its genetic polymorphisms may contribute to the aetiology and pathogenesis of disease in different ethnic groups. Polymorphisms in IL1β, IL18, NFKB1 and IFNG genes were studied in different populations with RA, but the analysis indicated contradictory results. Thereby, we hypothesised that polymorphisms in these genes could have a combined effect on susceptibility to and severity of disease. We evaluated the +3953 C/T IL1β (rs1143634), –137 G/C IL18 (rs187238), –94 ins/del ATTG NFKB1 (rs28362491) and +874 T/A IFNG (rs2430561) polymorphisms in the northeastern Brazilian population. Peripheral blood samples were collected and DNA extraction was conducted. The polymorphisms were evaluated by RFLP and ARMS–PCR. An association was observed in rs1143634 which showed a protective effect against development of RA in carriers of the T allele (OR = 0.58; 95% CI 0.36–0.92; p = .020). In addition, we found an association among genotypes of the rs1143634 with the HAQ index (p = .021) and rs2430561 with DAS28 (p = .029) and CDAI (p = .029). In relation to combined effects of these SNPs (C/C to rs1143634, G/G to rs187238, I/I to rs28362491 and AA to rs2430561) we found a significant association with decreased functional disability (HAQ index p < .001) and ESR (p = .034), indicating a lower disease activity in carriers of these genotypes. GLM analysis confirmed these associations (HAQ (F = 5.497; p < .001) and ESR (F = 2.727; p = .032)). Our analysis indicated that in the studied population +3953 C/T IL-1β (rs1143634), –137 G/C IL-18 (rs187238), –94 ins/del ATTG NFKB1 (rs28362491) and +874 T/A IFNG (rs2430561) polymorphisms can together contribute to RA severity although they do not individually influence the disease.

Human leukocyte antigen-G 3′ untranslated region polymorphism +3142G/C (rs1063320) and haplotypes are associated with manifestations of the American Tegumentary Leishmaniasis in a Northeastern Brazilian population

While the role of cytokine genes has been well documented in the context of Leishmania (Viannia) braziliensis infection, no studies have addressed the influence of human leukocyte antigen-G (HLA-G) in susceptibility/resistance to American Tegumentary Leishmaniasis (ATL). Here, we evaluated the influences of HLA-G, IL-10, TNF-A and IFN-G in the susceptibility and clinical manifestations of ATL.DNA of 114 ATL patients and 346 healthy individuals were sequenced for well-documented polymorphisms in HLA-G 3′ untranslated region (UTR), in IL-10 and TNF-A promoters and in IFN-G intron 1. Soluble HLA-G (sHLA-G) and cytokine levels were evaluated by ELISA and flow cytometry, respectively. Analyses were performed using GraphPad and R-package software.Individuals bearing HLA-G +3142G/G showed an association with increased risk for ATL, whereas those carrying the HLA-G +3142C/G and one copy of UTR6 haplotype, showed an association with decreased risk for ATL. sHLA-G was overexpressed in “susceptible” patients compared to the “resistant’’ one, and also in patients bearing +3142G/G genotype.From these results, HLA-G +3142G/G may be considered as genotype of susceptibility and UTR6 as marker of protection to ATL. Our findings showed a participation of HLA-G in the pathogenesis of the ATL.

Validation of the Third Molar Maturation Index to estimate the age of criminal responsibility in Northeastern Brazil

The estimation of the age of majority is crucial to determine the legal accountability of an individual. With this purpose, the analysis of the dental development process has proven to be an effective, elucidatory method. This study investigated the applicability of the Third Molar Maturation Index (I3M), proposed by Cameriere et al. (2008), to estimate the age of majority in a sample of Northeastern Brazilians using panoramic radiographs. Adobe® Photoshop® CS4 (Adobe Systems Incorporated, San Jose, California, USA) software was used to obtain the I3M index measurements in a sample of radiographs from a dental radiology clinic located in Northeastern Brazil. Radiographs of individuals aged between 14 and 23 years were included in the sample, except if showing absence, distortions, pathological alterations or suspected pulp impairment of the tooth #38 (third lower left molar), as the method applies exclusively to this element. Of the total sample of radiographs previously obtained for diagnostic and/or orthodontic purposes (n=394), 185 were from males and 209 from females, of which 217 corresponded to 18 year-olds or older and 177 were from minors. Logistic regression and predictive values of sensitivity, specificity and Receiver Operating Characteristic (ROC) curve (α=0.05) were used. The cutoff point originally proposed for the I3M index (0.08) presented a sensitivity of 88.4% and a specificity of 73.2%, with accuracy (area under the ROC curve) of 80.8% (95%CI: 76.4–85.3%) for the Northeastern Brazilian population, as well as a correct age classification in 80.2% of the sample. The method estimated accurately 73.7% of the cases corresponding to “18 years or older” and 88.1% of the cases “under 18years” (p=0.000). Among the sexes, the correct age classification rate of the method was 84.3% for males and 76.6% for females, with no statistically significant difference between the match and error rates and between the sexes (p≥0.05). In conclusion, the Third Molar Maturation Index could accurately distinguish the age of adolescents and young adults of both sexes aged 18 years or under/older in a Brazilian population.

Research Article Polymorphisms of the mannose binding lectin (&lt;i&gt;MBL2&lt;/i&gt;) gene are related to protein plasma levels but not with visceral leishmaniasis in a northeastern brazilian population

Research Article Polymorphisms of the mannose binding lectin (&lt;i&gt;MBL2&lt;/i&gt;) gene are related to protein plasma levels but not with visceral leishmaniasis in a northeastern brazilian population

Vitamin D receptor (VDR) polymorphisms are associated to spontaneous preterm birth and maternal aspects

Preterm birth (PTB) is featured by less than 37weeks of gestational age or fewer than 259days since the first day from the last menstrual period. Complications of PTB are the major cause of neonatal deaths, several factors are linked to PTB increased risk including immunological and genetics. Vitamin D plays an important role in immune response modulation and its action occurs through the vitamin D receptor (VDR), which recently has been described as overexpressed in human placenta during the pregnancy. Herein we assessed two single nucleotide polymorphisms (SNPs) FokI (rs2228570 A>G) and Cdx-2 (rs11568820 T>C), within VDR, using TaqMan fluorogenic probes, and differential susceptibility to SPTB. We assessed 104 pregnant women with SPTB and 85 women with normal birth in a Northeastern Brazilian population. Statistically significant differences for both SNPs where found when comparing allele and genotype frequencies in both groups: the T allele for rs2228570 and A allele for rs11568820 were significantly more frequent in SPTB group than in normal birth group (p=0.000013 and p=0.00466, respectively). The rs11568820 A/A genotype was associated to clinical/demographic variables such as: premature birth (p=0.007), neonate weight (p=0.039), presence of infection during pregnancy (p=0.011) and premature birth among multiparous (p=0.015). The rs2228570 T/T genotype associated with gestational diabetes mellitus (p=0.044) and chorioamnionitis during pregnancy (p=0.043). In conclusion our findings indicate an association between polymorphisms FokI and Cdx-2 within VDR gene and SPTB, suggesting their involvement in the triggering of these syndromes.

Environmental impacts caused by cemeteries and crematoria, new funeral technologies, and preferences of the Northeastern and Southern Brazilian population as for the funeral process.

Cemeteries and crematoria are the main funeral ways used in the world nowadays. It is a little-studied segment in the present days, mainly as for the possible environmental impacts in the environment, such as those derived from dental amalgam, prostheses, and dioxins, among other. This article aimed to identify the environmental impacts caused by cemeteries and crematoria and to point out new trends in funeral processes such as freeze-drying and alkaline hydrolysis. The study is justified due to the large part of the Brazilian population that do not know the environmental impacts caused by cemeteries and crematoria, as well as to bring information about the new processes. For that, a research was carried out with 400 people. The main results show that among all the funeral processes, the new freeze-drying process was opted by 33% of the sample. We also identified that the main reasons for choosing the funeral process were less environmental impact (28%), no after-death expenses (grave payment) (16.1%), and the possibility of putting away or throwing away the remains wherever you want (14.9%). Finally, new funeral processes were well accepted by the Brazilian population-those who were interviewed-due to their benefits.

MtDNA structure: the women who formed the Brazilian Northeast

BackgroundThe distribution of mitochondrial DNA (mtDNA) lineages in Brazil is heterogeneous due to different regional colonization dynamics. Northeastern Brazil, although being an important region in terms of human imigration and ethnic admixture, has little information regarding its population mtDNA composition. Here, we determine which mitochondrial lineages contributed to the formation of the Northeastern Brazilian population. Our sample consisted of 767 individuals distributed as follows i) 550 individuals from eight Northeastern states (Piauí, Ceará, Rio Grande do Norte, Paraíba, Pernambuco, Alagoas, Sergipe, and Bahia) which were sequenced for mtDNA hypervariable segments I, II, and III; ii) 217 individuals from Alagoas and Pernambuco (previously published data). Data analysis was performed through sequence alignment and Haplogrep 2.0 haplogroup assignment tools. Furthermore, maternal ancestry distribution was contextualized and, when possible, related to historical events to better understand the biological interactions and population dynamics that occurred in this region since the beginning of colonization.ResultsUnexpectedly, Amerindian mitochondrial ancestry was the highest in the Northeastern region overall, followed by African, European and non-Amerindian Asian, unlike previous results for this region. Alagoas and Pernambuco states, however, showed a larger African mtDNA frequency. The Northeastern region showed an intraregional heterogeneous distribution regarding ancestral groups, in which states/mesoregions located to the north had a prevalent Amerindian ancestral frequency and those to the south had predominance of African ancestry. Moreover, results showed great diversity of European haplogroups and the presence of non-Amerindian Asian haplogroups.ConclusionsOur findings are in disagreement with previous investigations that suggest African mitochondrial ancestry is the most prevalent in the Brazilian Northeast. The predominance of Amerindian lineages exemplifies the importance of indigenous women in the formation of the population, despite intense African slave entry and conflicts with European settlers. The variable distribution of ancestral groups observed in the Northeast is in accordance with historical records showing the similarities with colonization dynamics occurred in the Amazon region and the Brazilian Southeast. Moreover, the variety of European haplogroups suggests multiple origins of founding groups, specially those found in Western European populations.

Effect of dietary consumption as a modifier on the association between FTO gene variants and excess body weight in children from an admixed population in Brazil: the Social Changes, Asthma and Allergy in Latin America (SCAALA) cohort study.

Previous studies have shown associations of variants of the FTO gene with body weight, but none of these have involved Latin American populations with a high level of miscegenation, as is seen in the north-eastern Brazilian population. This study evaluated the association between SNP in the FTO gene and excess weight in Salvador, Bahia, Brazil. In addition, the effect of diet as a modifier on this association was also investigated. This cross-sectional study included 1191 participants aged 4-11 years, who were genotyped for 400 variants of the FTO gene. Direct anthropometric measures were made and dietary data were obtained by 24-h food recall. Multivariate logistic regression analyses were used to assess the associations of interest. Overall, 11·2 % of the individuals included in the study were overweight/obese. Interactions were identified between the percentage energy intake from proteins and obesity risk linked to the rs62048379 SNP (P interaction=0·01) and also between fat intake (PUFA:SFA ratio) and obesity risk linked to the rs62048379 SNP (P interaction=0·01). The T allele for the variant rs62048379 was positively associated with overweight/obesity in individuals whose percentage energy intake from protein was above the median (OR 2·00; 95 % CI 1·05, 3·82). The rs62048379 SNP was also associated with overweight/obesity in individuals whose PUFA:SFA ratio was below the median (OR 1·63; 95 % CI 1·05, 2·55). The association between FTO gene variants and excess body weight can be modulated by dietary characteristics, particularly by fatty acid distribution and dietary protein intake in children.

DEFB1 gene polymorphisms and tuberculosis in a Northeastern Brazilian population.

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).

Association of the XPD and XRCC3 gene polymorphisms with oral squamous cell carcinoma in a Northeastern Brazilian population: A pilot study

Objectiveto evaluate the association between XPD and XRCC3 polymorphisms and oral squamous cell carcinoma (OSCC). Designthe sample consisted of 54 cases of OSCC and 40 cases of inflammatory fibrous hyperplasia (IFH). Genotypes were determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. ResultsXPD-Lys/Gln was more common in IFH (n=28; 70%) than in OSCC (n=24; 44.4%) (OR: 0.3; p<0.05). XPD-Gln was more frequent in high-grade lesions (0.48) than in low-grade lesions (0.21) (OR: 3.4; p<0.05). The Gln/Gln genotype was associated with III and IV clinical stages (OR: 0.07; p<0.05). XRCC3-Met was more frequent in OSCC (0.49) than in IFH (0.35) (OR: 2.6; p<0.05). The Met/Met genotype was associated with the presence of metastases (OR: 8.1; p<0.05) and with III and IV clinical stages (OR: 0.07; p<0.05). Conclusionsin this sample, the frequency of XPD-Gln in IFH suggests that this variant may protect against OSCC. The presence of the XRCC3-Met allele seems to contribute to the development of OSCC, metastases and more advanced stages in these lesions.

Prevalence of syphilis, human immunodeficiency virus, hepatitis B virus, and human T-lymphotropic virus infections and coinfections during prenatal screening in an urban Northeastern Brazilian population

To evaluate prevalences of Treponema pallidum, human immunodeficiency virus (HIV), human T-lymphotropic virus (HTLV), and hepatitis B virus (HBV) infections and coinfections during prenatal screening in an urban Northeastern Brazilian population through a large dataset. Secondary data were obtained from the Maceió (Alagoas, Brazil) municipal prenatal screening program from June 2007 to May 2012. Dried blood serum tests from 54,813 pregnant women were examined to determine prevalences of T. pallidum, HIV, HTLV, and HBV infections and coinfections, and the seroconversion rates for syphilis and HIV infection. Socio-demographic variables associated with syphilis and HIV infection were identified. The prevalences of syphilis, HIV, HTLV, and HBV infections were 2.8%, 0.3%, 0.2%, and 0.4%, respectively. Pregnant women infected with T. pallidum had a 4.62-fold greater risk of HIV coinfection, and pregnant women infected with HIV had a 5.71-fold greater risk of T. pallidum coinfection. Seroconversion for syphilis and HIV during pregnancy occurred in 0.5% and 0.06% of women, respectively. Among the women carrying HTLV, 4.2% also had an HBV infection. Syphilis was twice as prevalent among pregnant women in Maceió, compared to the national average, and coinfections with syphilis/HIV and HTLV/HBV were significantly associated among these pregnant women.

Lack of association between the prothrombin rs1799963 polymorphism and juvenile myoclonic epilepsy.

Juvenile myoclonic epilepsy (JME) accounts for 26% of generalized idiopathic epileptic syndromes. The highest levels of thrombin activity are closely involved in the development of neurological diseases, including epilepsy. The prothrombin c.20210G>A (rs1799963) variation, which alters prothrombin mRNA stability, is associated with high plasma prothrombin levels. The present study was designed to investigate whether the SNP rs1799963 is a risk factor for JME in the northeastern Brazilian population. The polymorphism was genotyped in 207 controls and 123 patients using polymerase chain reaction-restriction fragment length polymorphism method. No significant differences were observed in the genotype and allele frequencies of this polymorphism between cases and controls. These results present no evidence for an association of rs1799963 with JME. Further studies including other types of epilepsy are required to investigate the involvement of prothrombin gene in the genetic susceptibility to chronic seizure.

Correlation of rheumatoid arthritis activity indexes (Disease Activity Score 28 measured with ESR and CRP, Simplified Disease Activity Index and Clinical Disease Activity Index) and agreement of disease activity states with various cut-off points in a Northeastern Brazilian population

IntroductionThe Disease Activity Score 28 (DAS28) and its versions have been used to measure rheumatoid arthritis activity, but there is no consensus about which one is the best. ObjectivesDetermine the correlation among indexes (DAS28 ESR, DAS28 CRP, SDAI and CDAI) and evaluate agreement of activity strata using different cut-off points. MethodsRheumatoid arthritis patients were cross-sectionally evaluated with data collection to calculate the DAS28 (ESR and CRP), SDAI and CDAI, using different cut-offs for defining remission, mild, moderate and high activity. Pearson correlations were calculated for continuous measures and agreement (kappa test) for the strata (remission, mild, moderate and high activity). ResultsOf 111 patients included, 108 were women, age 55.6 years, 11-year disease duration. DAS28 (ESR) was significantly higher than DAS28 (CRP) (4.0 vs. 3.5; p<0.001) and the values remained higher after stratification by age, gender, disease duration, rheumatoid factor and HAQ. Correlations among indexes ranged from 0.84 to 0.99, with better correlation between SDAI and CDAI. Agreements among activity strata ranged from 46.8% to 95.8%. DAS28 (CRP) with cut-off point for the remission of 2.3 underestimated disease activity by 45.8% compared with DAS28 (ESR). SDAI and CDAI showed agreement of 95.8%. The four indexes were associated with disease duration and HAQ. ConclusionsAlthough the activity indexes show good correlation, they show discrepancies in activity strata, thus requiring more researches to define a better index and better cut-off points.

Short Communication FYB polymorphisms in Brazilian patients with type I diabetes mellitus and autoimmune polyglandular syndrome type III.

The aim of this study was to perform an association study between seven Fyn-binding protein gene (FYB)-tag single nucleotide polymorphisms (SNPs) and type I diabetes mellitus (T1DM), as well as with disease age of onset. We also assessed the role of FYB SNPs in the insurgence of autoimmune polyglandular syndrome type III (APSIII), characterized by the simultaneous presence of autoimmune thyroid disease and celiac disease, in patients with T1DM from a Northeastern Brazilian population. One hundred and seventy-seven patients with T1DM and 190 healthy individuals were genotyped for seven tag SNPs, covering most of the FYB locus, using real-time polymerase chain reaction amplification. There was no significant difference in the distribution of allele and genotype frequencies among patients and healthy individuals. Moreover, none of the tag SNPs were associated either to T1DM age of onset or to the insurgence of APSIII. However, since the FYB protein is a key component in T cell response, its gene variants might play a role in protein function, which might be testable in a population with different genetic backgrounds or by using functional assays.

Association of MBL2 polymorphism with Leg Ulcers Development in Sickle Cell Anemia Patients

Leg ulcers are the most common clinical manifestations of sickle cell anemia (SCA), a monogenic disease with huge clinical diversity among patients. They affect 8% to 10% of SCA patients, reaching a percentage greater than 50% in patients residing in tropical areas. These ulcers occur due to vascular occlusion, tissue hypoxia, hemolysis and genetic factors, presenting a slow healing, high recurrence rate and huge susceptibility to infection. Recently, some studies have shown a positive relationship between the complement system and the development of some vascular diseases and injuries such as leg ulcers in non-SCA patients. Mannan-binding lectin (MBL) is an important component of the humoral innate immune system, and MBL possesses several characteristics indicating that it may play an essential role in wound healing; modulating inflammation and contributing to the clearance of microorganisms and apoptotic cells. In a recent study of chronic leg and foot ulcer patients, serum MBL levels were significantly different between wounds of different etiologies, with chronic venous leg ulcers patients having a higher frequency of MBL deficiency. Polymorphisms in the MBL2 are associated with a reduction in the MBL protein serum levels, increasing risk of developing leg ulcers and also the maintenance of these wounds, compromising the integrity of the immune defence and its response to potential invading pathogens. Here, we aimed to determine the frequency of polymorphisms in the promoter region -221 (Y / X) and -550 (H / L) and exon 1 of the MBL2 and assess the clinical impact of these variants in a northeastern Brazilian SCA population who presented leg ulcers. Two-hundred seventy-five unrelated SCA patients were included. According the leg ulcers presence, the total cohort was classified in patients presenting current or prior history of leg ulcers (n=100) and SCA patients above 18 years with no history of leg ulcers (n=175). Molecular analysis was performed by qPCR. Our population was in Hardy-Weinberg equilibrium. The allelic frequency of haplotypes associated with high MBL production (HYA, LYA) was 54.5% for cases and 62.9% in controls. The genotypes related to low MBL production (HYO, LYO) in cases and controls was 27.5% and 18.6%, respectively. The frequency of genotype related to intermediate MBL production (LXA) was 18% in cases and 18.5% in controls. We had no statistically significant results when we analyzed only the polymorphisms (P>0.05). However, the phenotypic analysis between high and low MBL production revealed that patients with leg ulcers have lower MBL protein levels (P=0.019). We focused specifically on a possible role of MBL deficiency on healing complications, based on the facts that MBL deficiency is the most common immune disorder, and that a common causality for prolonged healing of these ulcers is infection or colonization by bacteria. In our study, MBL deficiency appears to increase the risk of developing leg ulcers in SCA patients. DisclosuresNo relevant conflicts of interest to declare.

Association between ACVR2A and early-onset preeclampsia: Replication study in a Northeastern Brazilian population

IntroductionPreeclampsia is a complex and heterogeneous disease with increased risk of maternal mortality, especially for earlier gestational onset. There is a great inconsistency regarding the genetics of preeclampsia across the literature. The gene Activin A receptor, type IIA (ACVR2A), was reported as associated to preeclampsia in Australian/New Zealand and Norwegian populations. The goal of this study was to validate this genetic association in a Brazilian population. MethodsWe performed a case-control study using 693 controls and 613 cases (443 preeclampsia, 64 eclampsia and 106 HELLP syndrome), from a Northeastern Brazilian population. Five single nucleotide polymorphisms (SNPs) in ACVR2A were tested for association through multiple logistic regression models. ResultsThere was no statistical association with preeclampsia (per se), eclampsia or HELLP. However, by grouping preeclampsia in accordance to the gestational age at delivery, SNPs rs1424954 (OR = 1.86; 95% CI, 1.25–2.78; p = 0.002) and rs1014064 (OR = 1.77; 95% CI, 1.21–2.60; p = 0.004) were significantly associated with early onset preeclampsia (gestational age ≤ 34 weeks). The risk haplotype had a frequency of 0.468 in early preeclampsia compared to 0.316 in controls (p = 0.0008 and permuted p = 0.002). DiscussionActivin A receptors are important in decidualization, trophoblast invasion and placentation processes during pregnancy. The gene ACVR2A was associated with the more severe early onset preeclampsia. This finding supports the hypothesis of different pathogenic mechanisms contributing to the early- and late-onset preeclampsia.

NLRP3 polymorphism is associated with protection against human T-lymphotropic virus 1 infection

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.

Association of CD209 and CD209L polymorphisms with tuberculosis infection in a Northeastern Brazilian population.

Tuberculosis (TB) caused by Mycobacterium tuberculosis, is major cause of morbidity and mortality worldwide. So far, many candidate genes have been investigated for their possible association with TB. Dendritic cell-specific intercellular adhesion molecule 3 (ICAM-3) grabbing non-integrin (DC-SIGN) and Liver/lymph node-specific intercellular adhesion molecule-grabbing non-integrin (L-SIGN), encoded by CD209 and CD209L genes respectively, are known for binding to M. tuberculosis on human dendritic cells and macrophages. We screened 4 single nucleotide polymorphisms (SNPs) in the promoter region of CD209, namely -939G>A (rs735240), -871A>G (rs735239), -336A>G (rs4804803) and -139G>A (rs2287886) and tandem repeat polymorphisms in exon 4 of CD209 and CD209L genes looking for association with TB in a Northeastern Brazilian population (295 subjects, 131TB patients and 164 healthy controls). The -139G>A and -939G>A SNPs were associated with susceptibility to TB, and in particular with pulmonary and extra-pulmonary forms respectively. The -871A>G and -336A>G SNPs were associated, the first with protection to both pulmonary and extra-pulmonary TB, the latter only with the pulmonary form. An association between GGAG haplotype and protection to TB infection was also found. Also tandem repeat polymorphism in CD209L exon 4 was associated with TB infection. This study provides evidence of an association between CD209 and CD209L polymorphisms and TB development in a Brazilian population, suggesting that variations in these genes may influence the protection and susceptibility to infection caused by M. tuberculosis.

Preeclampsia is associated with increased maternal body weight in a northeastern Brazilian population

BackgroundPreeclampsia is a disease with great variability in incidence across the world. The mortality is higher in lower income countries, where it is the leading cause of maternal mortality. This study aimed to determine the frequency of and risk factors for preeclampsia in a low income population from an urban area of Brazil.MethodsA prospective case control study of 242 women of which 30 developed preeclampsia, 4 had gestational hypertension, 2 had superimposed hypertension, 11 had spontaneous abortion, 13 were lost to follow up and 192 had normal pregnancy. This latter group was considered the normotensive controls. The rate of preeclampsia and the risk of cardiovascular disease, after onset of preeclampsia, were determined.ResultsOf the 218 women who completed the study, the frequency of hypertensive disorder of pregnancy was 16.5% (36 of 218) and of preeclampsia was 13.8% (30 of 218). Women with preeclampsia had a higher body mass index (BMI), mean of 25.3 ± 4.8 compared to 23.5 ± 3.7 for the normotensive controls, p = 0.02. The risk of preeclampsia increased with BMI [Odds ratio (OR) 1.12, 95% Confidence Interval (CI = 1.02;1.24, p-value = 0.023)]. Women with preeclampsia developed chronic hypertension more often than normotensive controls (p = 0.043) and their systolic and ambulatory blood pressure monitoring was elevated (p = 0.034). Women with preeclampsia had higher BMI even 5 years post-pregnancy (p = 0.008).ConclusionsWomen who are overweight or older have an increased risk of preeclampsia. Previous history of preeclampsia increases the risk of early onset of chronic hypertension. Therefore, effective preventive measures are needed, particularly women at lower social economic stratum who have less access to proper medical care and adequate nutrition.