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OBJECTIVE: The aim of the study was to analyze the association between the superoxide dismutase 2 (SOD2) gene variants rs2758346, rs5746094, and rs2758331 and breast cancer (BC) in the Mexican population as well as to perform in silico assessments of the variants' potential impact. PATIENTS AND METHODS: We performed in silico analysis and analyzed 489 healthy women and 467 BC patients using TaqMan assays and Real-Time PCR. RESULTS: The TT genotype, the T allele of the rs2758346 variant, and the CC genotype of both rs5746094 and rs2758331 were identified as BC risk factors (p < 0.05). The TT and CTTT genotype of the rs2758346 variant stratified by the presence of ki-67 (> 20%), TCCC, and estrogen receptor (ER)-positive of the rs5746094 variant, and the CC and CT genotypes of rs2758331 stratified by menopause status and non-chemotherapy response were risk factors. The TTC and TTA haplotypes are risk factors for BC. In silico analysis revealed that the rs2758346, rs5746094, and rs2758331 variants could influence SOD2 gene regulation by transcription factors and circulating RNAs (circRNAs). CONCLUSIONS: The rs2758346, rs5746094, and rs2758331 variants of the SOD2 gene were associated with BC risk and could influence SOD2 regulation by transcription factors and circRNAs.
Assuntos
Neoplasias da Mama , Superóxido Dismutase , Feminino , Humanos , Neoplasias da Mama/genética , Neoplasias da Mama/epidemiologia , Estudos de Casos e Controles , Predisposição Genética para Doença , Genótipo , Polimorfismo de Nucleotídeo Único , Fatores de Risco , RNA Circular , Superóxido Dismutase/genética , Fatores de Transcrição/genéticaRESUMO
OBJECTIVE: Hunter syndrome, or mucopolysaccharidosis type II (MPS II), is caused by deficiency of the lysosomal enzyme iduronate-2-sulfatase (IDS), which is responsible for degrading heparan and dermatan sulfate. The IDS gene is located on chromosome Xq28; pathological variants in this gene mostly consist of missense mutations and small and larger deletions, which produce different phenotypes. However, there is only one record in our population concerning the molecular mechanism of this disease; a genotype-phenotype description is not available. PATIENTS AND METHODS: There were included 24 unrelated male patients; clinical features were recorded at a database, fluorometric IDS enzyme activity testing was done for each individual, followed by Sanger sequencing to identify mutations. RESULTS: The mutational spectrum was found in 16 out of 24 Mexican patients with MPS II, and its range of phenotypes was described. The most frequent variants were of the missense type. The most affected exons were exon 3 (c.275T>G, c.284_287del, c.325T>C), exon 8 (c.1035G>C, c.550G>A), exon 9 (c.1403G>C, c.1229_1229del), and exon 7 (c.979A>C; this variant has not been previously reported). Exon 5 (c.438C>T, a non-pathogenic variant) was the least frequent. It was also found that the most severely affected patients were those with large deletions (2 out of 24) [rsaIDS: IDSP1 (P164)x0, FMR1, AFF2 (P164)x2] involving genes and pseudogenes. We found 2 patients with a synonymous mutation in exon 4. CONCLUSIONS: Our results confirmed reports in the literature, since the most frequent variants were reported in exons 3 and 8. However, this result varies from one previous report in our population, which mentions large deletions and rearrangements as the most frequent alterations, since complex rearrangements were not found. According to what has been previously found, the most severely affected patients are those in which a whole gene has been deleted.
Assuntos
Iduronato Sulfatase , Mucopolissacaridose II , Proteína do X Frágil da Deficiência Intelectual/genética , Humanos , Iduronato Sulfatase/genética , Ácido Idurônico , Masculino , Mucopolissacaridose II/epidemiologia , Mucopolissacaridose II/genética , Mutação , FenótipoRESUMO
OBJECTIVE: Polymorphisms of the KRAS gene have been shown to be associated with cancer. However, their association with breast cancer (BC) has been inconsistent. The purpose of this study was to determine the frequency with which the rs61764370, rs9266, and rs140080026 polymorphisms of the KRAS gene are associated with BC in patients of the Mexican population. PATIENTS AND METHODS: The rs61764370 A>C or T>G and rs140080026 A>G polymorphisms were determined by Polymerase Chain Reaction (PCR), and the rs9266 A>G polymorphism was determined by DNA sequencing of healthy Mexican subjects and BC patients. RESULTS: We observed that 78% of BC patients are overweight and/or obese, 57% have metastatic lymph nodes, 64% have luminal A/B cancer subtypes, and 61% have stage III-IV cancer. The rs61764370 polymorphism was associated with BC susceptibility when the BC patients and the control group were compared for the AC genotype (pâ =â 0.020), AC vs. AA genotypes (heterozygous model: pâ =â 0.016), AC/CC genotype (dominant model: pâ =â 0.002), and the C allele (pâ =â 0.007). The AC/CC genotype (pâ =â 0.018; rs61764370) and AG/GG genotype (pâ =â 0.005; rs9266) were associated with age in BC patients ≥50 years old. The AC/CC (rs61764370) and AG/GG (rs9266) genotypes were classified by molecular subtype, TNM stage, miscarriage, lymph node metastasis, ductal type, and Ki-67. These classifications were also associated with BC patients, indicating that these factors may significantly contribute to BC risk. The AAA (OR 0.65, 95% CI 0.43-0.98, pâ =â 0.039) and CAA (OR 3.25, 95% CI 1.13-9.36, pâ =â 0.021) haplotypes were also associated with BC susceptibility. In addition, 94 polymorphisms were identified on the 3'UTR of the KRAS gene GRCh 38/hg3 (25,209,490-25,209,122) in BC (nâ =â 112) and control (nâ =â 113) samples. However, 92 of these polymorphisms have only expressed the major allele (wild-type allele). CONCLUSIONS: The rs61764370 polymorphism in the KRAS gene was associated with BC susceptibility in the Mexican population. The dominant model of the rs61764370 and rs9266 polymorphisms (classified by molecular subtype, miscarriage, TNM stage, lymph node metastasis, and Ki-67) could significantly contribute to BC risk in patients ≥50 years. The CAA haplotype could significantly contribute to BC risk in the Mexican population analyzed.
Assuntos
Neoplasias da Mama/genética , Hispânico ou Latino/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Adulto , Neoplasias da Mama/patologia , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , México/etnologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Polimorfismo de Nucleotídeo Único , RiscoRESUMO
OBJECTIVE: Primary outcome was to evaluate complete improvement at six months after acute treatment in NMOSD relapses. METHODS: Retrospective observational cohort study of patients with diagnosis of NMOSD admitted for acute attacks. We performed an explanatory analysis using the univariate, bivariate and multivariate logistic regression approach. We compared survival curves using the Kaplan Meier analysis and estimated the median time for the main outcome. RESULTS: In the univariate analysis, basal EDSS score, AQP4-IgG positivity, PLEX as a first-line treatment (IVMP + PLEX), less systemic complications related to acute treatment and total attack history were independently associated with complete improvement at six months. After adjusting for confounding variables and using multivariate analysis by Cox Regression, positive AQ4-IgG (HR 0.04, 95% CI: 0.02-0.66) and IVMP + PLEX (HR 5.1, 95% CI: 3.9-66.4), were kept as independent factors associated to time to complete improvement. Time from admission to PLEX initiation and complete improvement at six months had a median of seven days (95% CI: 5.2-8.8). In secondary effects, there were no statistical differences between the groups. CONCLUSIONS: PLEX + IVMP is the treatment of choice for NMOSD relapses and should be initiated as early as possible.
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Although acute stress generally exerts positive effects on the immune system, chronic stress typically causes immunosuppression via the hypothalamic-pituitary-adrenal (HPA) axis. In this study, the effects of capsaicin (1.28 mg/kg intraperitoneally [i.p.] for 7 days) on immune parameters were evaluated under conditions of chronic stress. Capsaicin treatment significantly increased the immune response as evaluated by the delayed-type hypersensitivity (DTH) reaction to dinitrofluorobenzene (DNFB) and splenocyte proliferation assays- It also is able to rescue the splenocytes of the apoptosis induced by stress. The capsaicin treatment increased the production of Th1 cytokines and decreased the production of Th2 cytokines and TGF-ß1 in the plasma and culture supernatants of immunosuppressed mice, which is associated with the modulation of Th2 induced by stress cells. Moreover, the production of corticosterone significantly decreased in capsaicin-treated animals as compared to control groups. The capsaicin treatment further attenuated the immunosuppression induced by the corticosterone treatment (40 mg/kg i.p. for 7 days), albeit less potently, as exhibited in the DTH response. Intriguingly, the capsaicin treatment decreased the induction of IL-10, IL-4, and TGF-ß1 through high doses of corticosterone, indicating direct cellular immunomodulation. These results show, that capsaicin is able to modulate chronic stress-induced immunosuppression, mediating corticosterone released inhibition, but also, that capsaicin significantly modulates the pharmacological action of corticosterone in vivo.
Assuntos
Capsaicina/farmacologia , Tolerância Imunológica/efeitos dos fármacos , Fatores Imunológicos/farmacologia , Estresse Fisiológico/efeitos dos fármacos , Animais , Proliferação de Células/efeitos dos fármacos , Corticosterona/farmacologia , Citocinas/sangue , Citocinas/imunologia , Dinitrofluorbenzeno , Hipersensibilidade Tardia/imunologia , Masculino , Camundongos Endogâmicos BALB C , Baço/citologia , Estresse Fisiológico/imunologia , Fator de Crescimento Transformador beta1/sangue , Fator de Crescimento Transformador beta1/imunologiaRESUMO
OBJECTIVE: The rs1008562, rs2234671 and rs3138060 polymorphisms of the CXCR1 gene have been shown to be associated with many diseases, but in breast cancer (BC) their association has not been detected. The purpose of this study was to determine the frequency and association of the rs1008562, rs2234671 and rs3138060 polymorphisms of CXCR1 gene in BC patients in the Mexican population. PATIENTS AND METHODS: The CXCR1 polymorphisms were determined by Polymerase Chain Reaction (PCR) and real time-PCR in healthy Mexican subjects and BC patients. RESULTS: The prevalent patron in BC patients was observed, the majority were overweight and obesity (72%) with metastatic lymph nodes (48%), luminal A/B subtypes (63%), and advanced stages (60%). Triple negative breast cancer (TNBC) patients: they were younger (58%) than 43 years old, overweight (33%), obesity (42%), ductal type histological (98%), metastasis to lymph nodes (47%), advanced stages III-IV (61%) and metastasis (33%). The rs2234671 polymorphism was associated with BC susceptibility when BC patients and the control group were compared for the CC genotype (p=0.037), CG (heterozygous model: p=0.018), GC/CC (dominant model: p=0.004), and the C allele (p=0.001), as well as the GC/CC genotype with hormone replace therapy (HRT, p=0.016). The rs3138060 polymorphism was associated with BC susceptibility for CG/GG genotype (dominant model: p=0.032) and G allele (p=0.018). Although the association between the dominant model of rs1008562, rs2234671, rs3138060 polymorphisms and BC patients and control was evident for tobacco and alcohol consumption (p<0.05). The rs1008562, rs2234671, and rs3138060 polymorphisms of the CXCR1 gene classified by molecular subtype and stage were also associated with BC patients, indicating that these factors may significantly contribute to BC risk. The CCC (OR 1.75, 95% CI 1.03- 2.97, p=0.046), GGG (OR 3.73, 95% CI 1.61- 8.65, p=0.0018) haplotypes were also associated with BC susceptibility. CONCLUSIONS: Rs2234671 and rs3138060 polymorphisms in the CXCR1 gene were associated with BC susceptibility in the Mexican population. The dominant model of the rs1008562, rs2234671 and rs3138060 polymorphisms could significantly contribute to BC risk in tobacco and alcohol consumption, molecular subtype and stage. The rs1008562, rs2234671 and rs3138060 polymorphisms, and the haplotypes CCC and GGG could significantly contribute to BC risk in the Mexican population analyzed.
Assuntos
Neoplasias da Mama/genética , Receptores de Interleucina-8A/genética , Adulto , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , México , Pessoa de Meia-Idade , Polimorfismo Genético , Grupos Raciais/genética , Fatores de RiscoRESUMO
OBJECTIVE: The rs2234694 and 50 bp insertion/deletion (Ins/Del) polymorphisms of the SOD1 gene have been shown to be associated with many diseases, but in breast cancer (BC) their association has not been detected. The purpose of this study was to determine the frequency and association of SOD1 gene polymorphisms (rs2234694 and 50 bp Ins/Del) in BC patients in the Mexican population. MATERIALS AND METHODS: The SOD1 polymorphisms were determined by Polymerase Chain Reaction (PCR) in Mexican healthy subjects and BC patients. RESULTS: The rs2234694 polymorphism was associated with BC susceptibility when BC patients and the control group were compared for the AC genotype (p<0.0001), the AC/CC genotype (dominant model: p<0.0001), and the C allele (p<0.0001). The 50 bp Ins/Del polymorphism was associated with BC susceptibility for the Del allele (p=0.048), although the association between the dominant model AC/CC (rs2234694) and BC patients was evident for menopause [adjusted odds ratio (OR) 1.65 (95% CI 1.05-2.7); p=0.048], Ki-67 (≥15%) (OR1.9, 95% CI 1.14- 3.16, p=0.016), and the presence of DM2 (OR 2.4, 95% CI 1.35- 4.31, p=0.003). A protective association for BC of the rs2234694 polymorphism was observed in patients younger than 50 years positive for estrogen receptor (ER) and progesterone receptor (PR), carrying the AC genotypes (OR 0.47, 95% CI 0.23-0.94, p= 0.033) and CC (OR 0.11, 95% CI 0.013-1.07, p=0.047). The association between the InsDel/DelDel (dominant model; 50 bp Ins/Del) genotype and BC with metastatic lymph nodes (OR 1.5, 95% CI 1.1-2.25, p=0.019), hematologic toxicity (OR 1.5, 95%CI 1.1-2.23, p=0.015), gastric toxicity (OR 1.5, 95%CI 1.1-2.07, p=0.030), and Ki-67 (≥15%) (OR1.6, 95%CI 1.2-2.26, p=0.002) was evident, indicating that these factors may contribute significantly to BC risk. The C/Ins haplotype was also associated with BC susceptibility (OR3.47, 95% CI 1.62-7.74, p=0.001). CONCLUSIONS: rs2234694 and 50 bp Ins/Del polymorphisms in the SOD1 gene were associated with BC susceptibility in a Mexican population. A protective association for BC of the rs2234694 polymorphism was observed in patients younger than 50 years positive for ER and PR, carrying the AC genotypes. The haplogenotypes AA/InsIns and AC/InsDel could contribute significantly to BC risk in gastric and hematologic toxicities, metastatic lymph nodes, and the presence of DM2 in the Mexican population analyzed.
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Neoplasias da Mama/genética , Polimorfismo Genético/genética , Superóxido Dismutase-1/genética , Alelos , Neoplasias da Mama/patologia , Feminino , Humanos , México , Pessoa de Meia-Idade , Fatores de Risco , Superóxido Dismutase-1/sangueRESUMO
BACKGROUND: Lupus is a chronic autoimmune and incurable rheumatic disease and has a global prevalence of 3.2-517.5 cases per 100,000 people. However, currently there is no knowledge regarding the actual direct cost of patients with lupus to healthcare systems in developing countries. This study aimed to determine the direct cost of lupus care in Colombia. METHODS: To identify patients with lupus, claims data of 2 years from two health insurers were subjected to an algorithm according to International Statistical Classification of Diseases and Related Health Problems 10th Revision codes. Multivariate linear regression analyses were used to assess the direct cost of lupus care. RESULTS: The average annual per-patient, all-claims, all-cause direct cost was $2355; this is approximately 9 times the average annual premium received by health insurers for covering the public benefits package. Approximately 50% of direct costs are not included in the public benefits package. The incidence of one or more condition is 98.4%. The direct cost incurred by patients with two comorbidities was 1.8 times more, with three chronic conditions was 1.9 times more and with six chronic conditions was 4.5 times more than that incurred by patients with only lupus. CONCLUSIONS: The direct cost of lupus care in the developing world may be higher than expected; in addition, access to healthcare may not be equal for the entire population.
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Custos de Cuidados de Saúde/estatística & dados numéricos , Lúpus Eritematoso Sistêmico/economia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Doença Crônica , Colômbia , Comorbidade , Efeitos Psicossociais da Doença , Países em Desenvolvimento , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Revisão da Utilização de Seguros/estatística & dados numéricos , Modelos Lineares , Lúpus Eritematoso Sistêmico/terapia , Masculino , Programas de Assistência Gerenciada/estatística & dados numéricos , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Adulto JovemRESUMO
Infectious pancreatic necrosis (IPN) is a widespread and economically devastating fish disease caused by infection with a virus referred to as IPN virus (IPNv). In Chile, the disease is endemic and prevalent in both fresh- and salt-water farms affecting cultured salmonids, mainly Atlantic salmon. Here, we present the results of a retrospective cohort study of Atlantic salmon farms stocked between 2010 and 2013, aimed at quantifying the extent to which certain epidemiological factors influence the time interval between stocking and onset of IPN mortality (time to mortality, ttm) in marine farms. Six variables were retained in a final multivariable Cox proportional hazard model. Compared to the 2010 stocking year, ttm was shorter for salmon stocked in years 2012 (HRâ¯=â¯2.1; pâ¯=â¯0.005) and 2013 (HRâ¯=â¯4.3; pâ¯=â¯0.01). The number of salmon farms within a 10-km radius (HRâ¯=â¯1.07; pâ¯=â¯0.002), positive report of IPN in the previous production cycle (HRâ¯=â¯1.95; pâ¯=â¯0.006), three or more smolt batches (HRâ¯=â¯2.27; pâ¯<â¯0.001), and positive report of mortality attributable to BKD (HRâ¯=â¯2.02; pâ¯<â¯0.001) were also associated with low ttm; conversely, ttm was longer for farms that stocked heavier fish (HRâ¯=â¯0.94; pâ¯=â¯0.001). The results presented here were consistent with early studies of IPN epidemiology in Norway and Scotland. Some of the risk factors identified in this study also influenced the risk for other diseases, such as infectious salmon anemia, suggesting that implementation of selected management practices may help to mitigate the burden of important infectious diseases of salmon in Chile.
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Infecções por Birnaviridae/veterinária , Vírus da Necrose Pancreática Infecciosa , Salmo salar , Animais , Infecções por Birnaviridae/epidemiologia , Infecções por Birnaviridae/virologia , Chile/epidemiologia , Estudos de Coortes , Estudos Retrospectivos , Fatores de RiscoRESUMO
AIM: Hyperhomocysteinemia has been associated with different pathologies, including cardiovascular diseases, hypertension, diabetes, and breast cancer (BC). To examine the differences in total homocysteine (tHcy) plasma levels, we compared healthy women to BC patients from a Mexican population. MATERIALS AND METHODS: The tHcy plasma levels were measured using high-performance liquid chromatography with a fluorescence detector in 89 female controls and 261 BC patients. RESULTS: The observed plasma tHcy levels were significantly higher among the BC patients (11.1019 ± 5.9161 µmol/l) compared to the controls (9.1046 ± 1.3213 µmol/l) (p = 0.002), and these differences were evident when stratified by age (≥ 50 years old), menopause status, overweight and obesity, miscarriages, node metastases, progression, subtype classification (luminal, Her2 and triple negative) and nonresponse to chemotherapy. CONCLUSIONS: The tHcy plasma levels could be a good marker for the progression and chemosensitivity of BC in the analyzed sample from a Mexican population.