The Impact of Variants in Four Genes: MC4R, FTO, PPARG and PPARGC1A in Overweight and Obesity in a Large Sample of the Brazilian Population.

Obesity and overweight are worldwide public health problems with an evident genetic predisposition that is still poorly understood. In addition, great variability has been described across populations. In this work, we analyzed the association of variants in four genes: PPARG (rs1801282), PPARGC1A (rs8192678), FTO (rs9939609) and MC4R (rs17782313) with overweight and obesity in a large sample of the Brazilian population. The case-control study involved 4084 individuals (1844 with overweight or obesity; and 2240 with normal BMI). Genotyping was performed by quantitative PCR. MC4R rs17782313-C was associated with obesity (OR = 1.27, p = 0.038) and when stratifying by sex associated only in women (OR = 1.36, p = 0.030). FTO rs9939609-A allele was associated with overweight however for women it represented a risk factor (OR = 1.24, p = 0.034) and for men, a protective factor (OR = 0.68, p = 0.033). PPARG was the strongest associated gene, with both overweight and obesity, and this association was also restricted to women (rs1801282-GG OR = 1.46, p = 0.027). The combined effect of the three risk alleles on overweight and obesity had an OR of 1.65 (p = 0.008) and when stratifying by sex again it was significant only in females (OR = 1.95, p = 0.0028). Our findings indicate that the three genes play a significant role in predisposing to overweight and/or obesity in the Brazilian population, reaching together a relatively high impact on these traits. Interestingly our results also suggest a strong sex-specific genetic effect of these variants.

Association of TNFRSF1A and IFNLR1 Gene Polymorphisms with the Risk of Developing Breast Cancer and Clinical Pathologic Features.

Several genes have been associated with breast cancer (BC) susceptibility. The tumor necrosis factor receptor superfamily, member 1A (TNFRSF1A), and interferon lambda receptor 1 (IFNLR1) genes encode receptors that mediate the action of inflammatory cytokines. Previous studies have demonstrated the association of the variants rs1800693 (TNFRSF1A) and rs4649203 (IFNLR1) with some inflammatory diseases. The present study aimed to verify a possible association of these variants with BC, its clinical pathologic features, as well as epidemiological data in a Brazilian population. A total of 243 patients and 294 individuals without history of BC were genotyped for these polymorphisms through TaqMan® SNP genotyping assays by qPCR. For the TNFRSF1A gene, no significant results were found. For IFNLR1, the AA genotype (p = 0.008) and the A allele (p = 0.02) were significantly associated with a lower risk of developing BC. When analyzing the age, it was observed that each increase of one year contributes to the development of BC (p < 0.001). Also, the smoking habit (p < 0.001) and body mass index (p = 0.018) increase the risk of disease development. Analyzing progesterone receptor factor an association was found with the AA genotype of the IFNLR1 (p = 0.02). The findings suggest that polymorphism in the immune-related IFNLR1 gene contribute to BC susceptibility in a Brazilian population. These findings can contribute to the further understanding of the role this gene and pathways in BC development.

Interferon III-related IL28RA variant is associated with rheumatoid arthritis and systemic lupus erythematosus and specific disease sub-phenotypes.

BACKGROUND: The interferon pathways have been commonly implicated in autoimmune disease development but the identity of the genes involved has not yet been fully clarified. Variation in genes involved in interferon pathways is expected to have a role in the etiology of these diseases. METHODS: The potential association of a polymorphism in the IL28RA gene, involved in these pathways, with susceptibility to systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) and disease-related phenotypes was investigated in 603 Brazilian individuals (354 well-characterized SLE and RA patients, and 249 controls). IL28RA (rs4649203) variant was genotyped by TaqMan assay. Statistical analysis was performed including both diseases and a comprehensive list of patient clinical manifestations. RESULTS: The rs4649203-G (minor) allele was associated with SLE and RA occurrence and was shown to be a risk factor for serositis and anemia among SLE patients as well as a protective factor for rheumatoid vasculitis and rheumatoid nodules in RA patients, suggesting an association with a milder form of the disease. CONCLUSIONS: The IL28RA gene may contribute to SLE and RA susceptibility and to specific clinical manifestations of the diseases.

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.

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.