Gene Expression of ABHD6, a Key Factor in the Endocannabinoid System, Can Be Modulated by Female Hormones in Human Immune Cells.

One of the main risk factors for the development of an autoimmune disease is to be a woman. Much attention has been given to the involvement of female hormones in their etiology and sexual bias, although the mechanisms behind this potentially strong contribution in disease susceptibility are poorly understood. ABHD6 gene was recently identified as a risk factor for system lupus erythematosus and the risk was correlated with overexpression of the gene. ABHD6 is an enzyme that degrades the 2-arachidonoylglycerol, an endocannabinoid with immunomodulatory effects. Thus its degradation could contribute to immune dysregulation and development of autoimmune reactions. Sex hormones, such as estrogens, are believed to regulate important genes in the endocannabinoid pathway. However, no study was available regarding the effect of these hormones in human immune cells. In this study, ABHD6 expression was evaluated by quantitative PCR in leukocytes from healthy male and females and in the presence of estrogen or progesterone (PG). A statistical increase in ABHD6 expression could be detected in women. In the presence of estrogen or PG, a statistical upregulation of ABHD6 was observed, and in a sex-dependent manner, as only female cells responded to stimulation. Our results suggest that female hormones can promote the overexpression of ABHD6 in immune cells. This can potentially contribute to a pro-inflammatory scenario and partially explain the association of this gene in the development of LES, a highly female-biased disease.

Population genetic data and forensic parameters of 30 autosomal InDel markers in Santa Catarina State population, Southern Brazil.

The application of DNA technology in forensic investigations has grown rapidly in the last 25 years and with an exponential increase of short tandem repeats (STRs) data, usually presented as allele frequencies, that may be later used as databases for forensic and population genetics purposes. Thereby, classes of molecular markers such as single nucleotide polymorphisms and insertions/deletions (InDels) have been presented as another option of genetic marker sets. These markers can be used in paternity cases, when mutations in STR polymorphisms are present, as well as in highly degraded DNA analysis. In the present study, the allele frequencies and heterozygosity (H) of a 30 InDel markers set were determined and the forensic efficacy was evaluated through estimation of discrimination power (DP), match probability, typical paternity index and power of paternity exclusion in 108 unrelated volunteers from the State of Santa Catarina (South Brazil). The observed H per locus showed a range between 0.370 and 0.574 (mean = 0.479). HLD128 was the locus with the highest DP (DP = 0.656). DP for all markers combined was greater than 99.9999999999646 % which provides satisfactory levels of information for forensic demands. Genetic comparisons (exact tests of population differentiation and pairwise genetic distances) revealed that the population of Santa Catarina State differs from Korea and USA Afro-American populations but is similar to the Portuguese, German, Polish, Spanish and Basque populations.

Influence of ACTN3 R577X Polymorphism on Blood Creatine Kinase Levels Relative to Number of Sprints in Brazilian Professional Soccer Players.

This study sought to assess how post-game creatine kinase (CK) levels correlate with the number of sprints and the impact of the ACTN3 polymorphism on this response. This research constituted a descriptive/observational, retrospective cross-sectional study. DNA was extracted from blood samples for ACTN3 polymorphism genotyping. CK was measured 48 h after official matches, and the number of sprints (>19 km/h) was tracked using Global Positioning System (GPS) technology. The main cohort included 23 professional soccer players from the top tier of the Brazilian Championship. We analyzed 115 GPS + CK data sets. The replication cohort comprised 18 professional soccer players from the First Division of the Championship, had the same methodology applied, and featured a total of 90 GPS (sprints > 25.2 km/h) + CK data sets. For the main cohort, a significant positive correlation was seen between the number of sprints and the CK levels (p = 0.009). Athletes with the ACTN3 RR genotype had higher CK levels as more sprints were performed during the match (p = 0.017). However, the relationship was not found for X allele carriers (p > 0.05). For the replication cohort, there was a near-significant correlation between CK levels and the number of sprints (p = 0.05), and RR individuals showed a significant association (p = 0.01), whereas X allele carriers did not (p = 0.06). A greater number of sprints during matches is linked to higher CK levels, primarily among players with the ACTN3 RR genotype, which is potentially due to an increased presence of type II muscle fibers. These findings were replicated for both cohorts of elite Brazilian soccer players, emphasizing the importance of genetic factors in injury prevention.

A Pilot Study on the Prediction of Non-Contact Muscle Injuries Based on ACTN3 R577X and ACE I/D Polymorphisms in Professional Soccer Athletes.

Muscle injuries are among the main reasons for medical leavings of soccer athletes, being a major concern within professional teams and their prevention associated with sport success. Several factors are associated with a greater predisposition to injury, and genetic background is increasingly being investigated. The aim of this study was to analyze whether ACTN3 R577X and ACE I/D polymorphisms are predictors of the incidence and severity of muscle injury in professional soccer athletes from Brazil, individually and in association. Eighty-three professional athletes from the first and second divisions of the Brazilian Championship were evaluated regarding the polymorphisms through blood samples. Nighty-nine muscle injuries were identified during the seasons of 2018, 2019 and 2020 and categorized according to severity. ACTN3 XX individuals had a higher frequency of severe injuries compared to the RX and RR genotypes (p = 0.001), and in the dominant model (compared to RX+RR), with p < 0.001. The trend p-value test showed an increased number of injuries/season following the order XX > RX > RR (p = 0.045). Those with the ACE II genotype had almost 2 fold the number of injuries per season compared to those with the ID+DD genotypes (p = 0.03). Logistic regression showed that the polymorphisms are predictors of the development of severe injury (ACTN3 R577X model with p = 0.004, R2: 0.259; ACE I/D model with p = 0.045, R2: 0.163), where ACTN3 XX individuals were more likely to suffer from severe injury (OR: 5.141, 95% CI: 1.472-17.961, p = 0.010). The combination of the ACTN3 577X allele and the ACE II genotype showed an increased number of injuries per season, enhanced by 100% (1.682 injuries/season versus 0.868 injuries/season, p = 0.016). Our findings suggest that both polymorphisms ACTN3 R577X and ACE I/D (and their interaction) are associated with the susceptibility and severity of non-contact muscle injury in soccer players.

Pre- and post-Columbian gene and cultural continuity: the case of the Gaucho from southern Brazil.

OBJECTIVE: To investigate the evolutionary and demographic history of the Gaucho, a distinct population of southern Brazil, relating it to their culture, to assess possible parallel continuity. METHODS: Six binary polymorphisms, an Alu insertion polymorphism (YAP) and 12 short tandem repeat loci in the non-recombining region of the Y-chromosome, as well as the sequence of the first hypervariable segment (HVS-I) of the mitochondrial DNA (mtDNA) control region were studied in 150 unrelated males born in the Pampa region of Rio Grande do Sul. RESULTS: Comparison of the results with the other Brazilian and Uruguayan populations, as well as with their putative ancestors, indicated a stronger male Spanish influence than that observed elsewhere in Brazil, a former Portuguese colony. Extensive mtDNA analyses of their Amerindian component gave clear indications of the presence there of material from extinct (Charrua), as well as extant (Guarani) tribes. CONCLUSIONS: The genetic analyses contributed in a significant way to reveal that the known cultural continuity between pre- and post-Columbian Pampa populations was also accompanied by an extraordinary genetic continuity.

DNA barcoding reveals the mislabeling of fish in a popular tourist destination in Brazil.

The consumption of raw fish has increased considerably in the West, since it is said to be potentially healthier than processed fish (for containing omega 3 and 6, essential amino acids and vitamins). However this potential benefit, as well as the taste, value and even the risk of extinction are not the same for all species of fish, constituting grounds for fraud. Using the principles of the DNA barcode we revealed mislabelling of fish in Japanese restaurants and fishmarkets in Florianópolis, a popular tourist capital in Brazil. We sequenced the COI gene of 65 samples from fisheries and 80 from restaurants and diagnosed 30% of mislabeled samples in fisheries and 26% in restaurants. We discussed that frauds may have occurred for different reasons: to circumvent surveillance on threatened species; to sell fish with sizes smaller than allowed or abundant species as being a much rarer species (law of supply); to induce product consumption using species with better taste. It should be noted that some substitutions are derived from incorrect identification and are not a fraud per se; they are due to confusion of popular names or misunderstanding by the sellers. Therefore, we suggest the implementation of a systematic regulatory program conducted by governmental agencies to reduce mislabelling in order to avoid further damage to the community (in health and financial issues) and fish stocks.

Lack of association between interleukin-18 polymorphisms and rheumatoid arthritis.

OBJECTIVE: To assess the association of the polymorphisms of the interleukin-18 (IL-18) gene with rheumatoid arthritis (RA) and with risk factors for cardiovascular diseases (CVD). METHODS: This sample comprised 97 patients with RA and 151 healthy controls. In the patients, risk factors for CVD were analyzed, such as cholesterol levels, arterial hypertension, smoking habit, C-reactive protein (CRP) level, and rheumatoid factor. DNA was extracted and the single nucleotide polymorphisms (SNP) at the -607C/A and -137G/C positions of the IL-18 gene were assessed in both groups. The Hardy-Weinberg equilibrium (HWE) was calculated and the odds ratio (OR) test performed, considering a 95% CI and P < 0.05. RESULTS: The frequencies of the -607A allele in patients with RA and in controls were 0,443 and 0.424, respectively, and of the -137C allele, 0.304 and 0.291, respectively. The genotype frequencies were in HWE, except for controls in the -137 locus (P = 0.006). Association of the polymorphisms of the IL-18 gene was found with neither RA nor risk factors for CVD, including cholesterol level and CRP (P > 0.05). In addition, more smokers were found among patients with RA as compared with controls (OR = 1.691; P = 0.088), and the CRP levels were slightly higher in patients who smoked than in patients who did not (OR = 2.673; P = 0.061). CONCLUSIONS: In this sample of patients with RA in the South of Brazil, association of the polymorphisms of the IL-18 gene was observed with neither RA nor risk factors for CVD.

Ausência de associação entre os polimorfismos do gene interleucina-18 e artrite reumatoide / Lack of association between interleukin-18 polymorphisms and rheumatoid arthritis

OBJETIVO: Analisar a associação dos polimorfismos do gene interleucina-18 (IL-18) com artrite reumatoide (AR) e com fatores de risco de doenças cardiovasculares (DCV). MÉTODOS: A amostra foi constituída por 97 pacientes com AR e 151 controles saudáveis. Nos primeiros, foram analisados fatores de risco de DCV, tais como níveis do colesterol, hipertensão arterial, tabagismo e fator reumatoide, bem como o nível da proteína C-reativa (CRP). O DNA foi extraído e foram analisados os polimorfismos de nucleotídeo único (SNP) nas posições -607C/A e -137G/C do gene IL-18 em ambos os grupos. O equilíbrio de Hardy-Weinberg (EHW) e o odds ratio (OR) foram realizados, considerando IC 95% e P < 0,05. RESULTADOS: As frequências do alelo -607A nos pacientes com AR e nos controles foram de 0,443 e 0,424 e do alelo -137C foram de 0,304 e 0,291, respectivamente. As frequências do genótipo estavam em EHW, exceto em controles no locus -137 (P = 0,006). Não foi encontrada associação dos polimorfismos do gene IL-18 com AR, nem com fatores de risco de DCV, incluindo o nível do colesterol e de CRP (P > 0,05). Além disso, observaram-se mais indivíduos fumantes entre pacientes com AR em comparação aos controles (OR = 1,691; P = 0,088), e os níveis de CRP eram ligeiramente mais elevados em pacientes fumantes quando comparados aos de pacientes não fumantes (OR = 2,673; P = 0,061). CONCLUSÕES: Ao analisar uma amostra de pacientes com AR no sul do Brasil, não foi encontrada associação dos polimorfismos do gene IL-18 com AR, nem com os fatores de risco de DCV.

OBJECTIVE: To assess the association of the polymorphisms of the interleukin-18 (IL-18) gene with rheumatoid arthritis (RA) and with risk factors for cardiovascular diseases (CVD). METHODS: This sample comprised 97 patients with RA and 151 healthy controls. In the patients, risk factors for CVD were analyzed, such as cholesterol levels, arterial hypertension, smoking habit, C-reactive protein (CRP) level, and rheumatoid factor. DNA was extracted and the single nucleotide polymorphisms (SNP) at the -607C/A and -137G/C positions of the IL-18 gene were assessed in both groups. The Hardy-Weinberg equilibrium (HWE) was calculated and the odds ratio (OR) test performed, considering a 95% CI and P < 0.05. RESULTS: The frequencies of the -607A allele in patients with RA and in controls were 0,443 and 0.424, respectively, and of the -137C allele, 0.304 and 0.291, respectively. The genotype frequencies were in HWE, except for controls in the -137 locus (P = 0.006). Association of the polymorphisms of the IL-18 gene was found with neither RA nor risk factors for CVD, including cholesterol level and CRP (P > 0.05). In addition, more smokers were found among patients with RA as compared with controls (OR = 1.691; P = 0.088), and the CRP levels were slightly higher in patients who smoked than in patients who did not (OR = 2.673; P = 0.061). CONCLUSIONS: In this sample of patients with RA in the South of Brazil, association of the polymorphisms of the IL-18 gene was observed with neither RA nor risk factors for CVD.

Niger-Congo speaking populations and the formation of the Brazilian gene pool: mtDNA and Y-chromosome data.

We analyzed sequence variation in the mitochondrial DNA (mtDNA) hypervariable segment I (HVS-I) from 201 Black individuals from two Brazilian cities (Rio de Janeiro and Porto Alegre), and compared these data with published information from 21 African populations. A subset of 187 males of the sample was also characterized for 30 Y-chromosome biallelic polymorphisms, and the data were compared with those from 48 African populations. The mtDNA data indicated that respectively 69% and 82% of the matrilineages found in Rio de Janeiro and Porto Alegre originated from West-Central/Southeast Africa. These estimates are in close agreement with historical records which indicated that most of the Brazilian slaves who arrived in Rio de Janeiro were from West-Central Africa. In contrast to mtDNA, Y-chromosome haplogroup analysis did not allow discrimination between places of origin in West or West-Central Africa. Thus, when comparing these two major African regions, there seems to be higher genetic structure with mtDNA than with Y-chromosome data.

Heterogeneity of the genome ancestry of individuals classified as White in the state of Rio Grande do Sul, Brazil.

One hundred nineteen individuals classified as White, living in different localities of the Brazilian state of Rio Grande do Sul, were studied in relation to the HVS-I region of the mitochondrial DNA (mtDNA). The male fraction of the sample (N = 74) was also tested for seven Y-chromosome polymorphisms. In a specific population (Veranópolis), a city characterized by a large influence of the Italian immigration of the 19th century, the results from the maternal and paternal sides indicated almost complete European ancestry. However, another sample identified as White, from different localities of Rio Grande do Sul, presented significant fractions of Native American (36%) and African (16%) mtDNA haplogroups. These results indicate that Brazilian populations are remarkably heterogeneous; while some present an overwhelming majority of transplanted European genomes, with a complete correspondence between physical appearance and ancestry, others reflect a history of extensive admixture with dissociation between physical appearance and ancestry.