Variants rs2758346, rs5746094, and rs2758331 of SOD2 gene: association study with breast cancer in a Mexican population and their analysis in silico.

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.

Association of the C677T polymorphism in the methylenetetrahydrofolate reductase gene with breast cancer in a Mexican population.

The methylenetetrahydrofolate reductase (MTHFR) gene plays an important role in the steps involved in the processing of amino acids. The analysis of polymorphisms in the MTHFR gene has revealed associations with cancer; in particular the C677T polymorphism, which has been suggested to affect folate metabolism, DNA methylation, synthesis, and repair, and to contribute to tumor promotion in the mammary gland. We examined the role of the C677T polymorphism in the MTHFR gene by comparing the C677T genotypes of 339 healthy Mexican women with those of 497 Mexican women with breast cancer (BC). The genotype frequencies observed in the controls and patients with BC were 10 and 21% for 677TT; 41 and 36% for 677CT; and 49 and 43% for 677CC, respectively. The odds ratio (OR) for the 677TT genotype was 2.5, with a 95% confidence interval (95%CI) of 1.6-3.8; P = 0.0001. The positive association was also evident when the distributions of the 677TT genotype in control and patients affected within the following two categories were compared to alcohol consumption (OR = 0.41; 95%CI = 0.19-0.86; P = 0.018); and high level glutamate-oxaloacetate transaminase (SGOT) (OR = 0.36; 95%CI = 0.15-0.83, P = 0.017). These results suggest that the 677TT genotype of the C677T polymorphism in the MTHFR gene is associated with BC susceptibility in the Mexican population.

Pulmonary function in ankylosing spondylitis: association with clinical variables.

To evaluate the association between pulmonary function and clinical variables in ankylosing spondylitis (AS) and to compare the pulmonary function of patients with AS with that of healthy controls, 61 AS patients and 74 healthy controls were included. In AS, we assessed clinical disease indices (BASDAI, BASFI, BASG), morning stiffness, number of hypersensitive entheses, metrology measures, 6-min walking test, acute phase reactants, radiological presence of "bamboo spine," and severity of radiological involvement in sacroiliac and vertebral joints. AS and healthy controls had similar age and gender. All the parameters of pulmonary function were significantly diminished in AS than in healthy controls (p < 0.001), with a higher proportion of restrictive pattern (57.4 vs. 5.4 %). In AS, pulmonary function correlated negatively with BASDAI, BASFI, BASG, morning stiffness, number of hypersensitive entheses, occiput-wall distance, and ESR, and positively with 6-min walking test. There was no association between pulmonary function with radiological stage of vertebral joints and sacroiliac joints, "bamboo spine," disease duration, or chest expansion. A higher frequency of AS patients had a decreased pulmonary function and results of the 6-min walking test. These abnormalities in AS were more related with disease activity than with mobility limitation.

The ACTN3 R577X polymorphism is associated with inflammatory myopathies in a Mexican population.

BACKGROUND: The ACTN3 gene encodes the fast muscle protein α-actinin-3. The ACTN3 R577X polymorphism is a premature stop codon and results in absence of α-actinin-3 in 577XX homozygotes. The aim of this study was to determine the ACTN3 genotype in idiopathic inflammatory myopathies (IIMs). METHODS: We performed ACTN3 genotyping on 27 patients with dermatomyositis (DM), 10 with polymyositis (PM), and 85 healthy subjects. Muscle enzyme levels of creatine phosphokinase (CPK), lactic dehydrogenase (LDH), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were recorded at the time of diagnosis and recruitment. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and the allele frequency was analysed. RESULTS: A total of 36% of healthy subjects had the ACTN3 577XX polymorphism (α-actinin-3 deficiency), 18% had the 577RR (homozygous wild type) genotype, and 46% 577RX (heterozygous). In DM/PM, 70% had the ACTN3 577XX polymorphism, 6% RR, and 24% RX [odds ratio (OR) 4.12, 95% confidence interval (CI) 1.67-10.33, p < 0.001]. In healthy subjects, the R allele was present in 41% and the X allele in 59% compared to 18% and 82%, respectively, in the IIM group (OR 3.21, 95% CI 1.57-6.66, p < 0.001). Thus, the ACTN3 577X allele seemed to increase the risk of developing IIM, and DM in particular, although this was not related to severity of expression of the phenotype. CONCLUSIONS: The ACTN3 577X allele appeared to increase the risk of developing IIM; 70% of IIM patients were deficient in α-actinin-3. By contrast, ACTN3 577XX patients seemed to have less severe disease as reflected in lower muscle enzyme levels.

Autoantibodies to a miRNA-binding protein Argonaute2 (Su antigen) in patients with hepatitis C virus infection.

OBJECTIVES: Chronic liver diseases caused by hepatitis B (HBV) or C virus (HCV) are common worldwide. Despite reports on autoimmunity in viral hepatitis, studies on autoantibodies associated with systemic rheumatic diseases are inconsistent. Testing of a small number of selected autoantibody specificities using ELISA appears to be one reason for inconsistency. Sera from patients with viral hepatitis were tested by immunoprecipitation that will allow unbiased screening of autoantibodies found in systemic rheumatic diseases. METHODS: Ninety Mexican patients (37 male, 53 female, 26 HBV, 6 HBV+HCV, 58 HCV) with chronic viral hepatitis, confirmed by nested or RT-nested-PCR, HBsAg and anti-HCV antibodies, were studied. Autoantibodies were tested by immunofluorescence, immunoprecipitation and ELISA. Specificities were verified using reference sera. RESULTS: Antinuclear antibodies were found in 38% HBV, 17% HBV+HCV, and 28% in HCV. Autoantibodies to Argonaute (Ago2, Su antigen), a microRNA binding protein that plays a key role in RNA-induced silencing complex (RISC), was found in 5% (4/64) of HCV or HBV+HCV coinfected patients but not in HBV (0/26). Anti-Ago2/Su was found in 1/2 of I-IFN-treated case vs. 3/62 in cases without I-IFN. HCV did not have other lupus autoantibodies whereas 19% (5/26) of HBV had anti-U1RNP+Ku, Ro+La, RNA polymerase II, or possible U5snRNPs. CONCLUSIONS: Lupus autoantibodies were uncommon in HCV except anti-Ago2/Su. HCV and I-IFN have many ways to affect TLR signaling, miRNA and miRNA binding protein Ago2/Su. To understand the mechanism of specific targeting of Ago2 in HCV may provide a clue to understand the mechanism of specific autoantibody production.

A teenager with a t(X;17)(q22;q25) and ovarian failure.

BACKGROUND: The effects of a balanced X; Autosome translocation [t(X;A)] on the fertility of carrier females led to the definition of the Xq13-->q27 region as critical for ovarian function and reproductive lifespan. We describe here a teenager with ovarian failure likely due to a balanced t(X;17)(q22;q25). CASE: The 16 year-old patient presented with secondary amenorrhea. She exhibited height of 164 cm, slender habitus, and sexual development Tanner 2. METHODS: Hormonal determinations, GTG- and RBG-banded karyotypes, fluorescence in situ hybridization, and human androgen receptor assay. RESULTS: FSH of 141 mIU/ml and LH of 46 mIU/ml); karyotype 46,X,t(X;17)(q22;q25)[30].ish der(X)t(X;1 7)(17qsubt el+); skewed inactivation of the normal X which was the maternal one as shown by the HUMARA assay. The maternal chromosomes were 46,XX; the father was unavailable. CONCLUSIONS: The patient's (X;17) translocation likely accounts for her ovarian failure via an epigenetic downregulation of ovary expressed 17q25 genes relocated next to the Xq21 POF Critical Region 1 and related to ovarian development and function. Her otherwise inconspicuous phenotype agrees with the preferential inactivation of the normal X-chromosome that preserves the gene homeostasis in women with a balanced t(X;A). Finally, the normal maternal karyotype along with the HUMARA results and the sterility of males carrying a t(X;A) strongly suggests that this t(X;17) was a paternal de novo mutation.

Chromosomal abnormalities in patients with azoospermia in Western Mexico.

In order to assess the frequency of chromosomal abnormalities in azoospermic males from western Mexico, we carried out a retrospective study in 227 patients. Forty-three (18.9%) cases with an abnormal karyotype were found. The most frequent chromosomal anomaly was 47,XXY, which was identified in 35 subjects (15.4%). In six cases (2.6%), structural aberrations were detected: two Robertsonian translocations [(45,XY,t(13;22)(p11;p11) and (45,XY,t(13;15)(p11;p11)], a Y;autosome translocation [46,XY,der(15)t(Y;15)(q12;p11)], and three mosaics [mos45,X/46,X,idic(Y)(q11)]. In general, these findings are in accordance with those from other surveys and confirm that the XXY aneuploidy is the most frequent chromosomal abnormality in azoospermic individuals.