ABSTRACT. The major pathological hallmark of the systemic sclerosis (SSc) is skin and internal organ fibrosis, which results from normal tissue architecture alterations and extracellular matrix (ECM) protein deposition. ECM components are degraded by matrix metalloproteinases (MMP). Promoter region polymorphisms in MMP genes may influence gene expression, resulting in an imbalance between ECM protein production and degradation. Here, we analyzed MMP1 -1607 1G/2G (rs1799750), MMP3 -1171 5A/6A (rs3025058), and MMP9 -1562 C/T 2 T.F. Rech et al. Genetics and Molecular Research 15 (4): gmr15049077(rs3918242) polymorphisms in relation to susceptibility to SSc and its clinical features. The patient group included 98 individuals with longstanding or recently diagnosed disease, meeting the American College of Rheumatology or LeRoy and Medsger criteria for SSc; the control group included 100 healthy blood donors. All participants were of European descent. Genotyping was performed by polymerase chain reaction followed by restriction digestion. Genotype and allele frequencies of MMP polymorphisms were similar between the two groups. In secondary analyses, significantly higher frequency of 1G/2G genotype from MMP1 polymorphism was observed for patients testing positive for antinuclear autoantibodies (P = 0.007), while 1G/1G genotype was associated with interstitial lung disease development (P = 0.018). The 6A/6A genotype from MMP3 polymorphism was absent in patients with calcinosis (P = 0.011), while the MMP3 5A/5A genotype correlated with the presence of anti-topoisomerase I antibodies (P = 0.009) and reduced diffusing capacity for carbon monoxide (P = 0.024). These results suggest that MMP polymorphisms are not associated with SSc susceptibility, although MMP1 and MMP3 variants are associated with specific SSc clinical and laboratory features.

Systemic lupus erythematosus (SLE) is an autoimmune chronic inflammatory disease that presents several clinical manifestations, affecting multiple organs and systems. Immunological, environmental, hormonal and genetic factors may contribute to disease. Genes and proteins involved in metabolism and detoxification of xenobiotics are often used as susceptibility markers to diseases with environmental risk factors. Cytochrome P450 (CYP) enzymes activate the xenobiotic making it more reactive, while the Glutathione S-transferases (GST) enzymes conjugate the reduced glutathione with electrophilic compounds, facilitating the toxic products excretion. CYP and GST polymorphisms can alter the expression and catalytic activity of enzymes. This study aimed to investigate the role of genetic variants of CYP and GST in susceptibility and clinical expression of SLE, through the analysis of GSTM1 null, GSTT1 null, GSTP1*Ile105Val, CYP1A1*2C and CYP2E1*5B polymorphisms. 371 SLE patients from Hospital de Clínicas de Porto Alegre and 522 healthy blood donors from southern Brazil were evaluated. GSTP1 and CYP variants were genotyped using PCR-RFLP and GSTT1 and GSTM1 variants were analyzed by multiplex PCR. Among European-derived individuals, a lower frequency of GSTP1*Val heterozygous genotypes was found in SLE patients when compared to controls (p = 0.005). In African-derived SLE patients, the CYP2E1*5B allelic frequency was higher in relation to controls (p = 0.054). We did not observe any clinical implication of the CYP and GST polymorphisms in patients with SLE. Our data suggest a protective role of the GSTP1*Ile/Val heterozygous genotype against the SLE in European-derived and a possible influence of the CYP2E1*5B allele in SLE susceptibility among African-derived individuals.

This study suggests that the CT genotype of the interleukin-1beta -31 C/T polymorphism plays a role in the successful eradication of H. pylori among patients with functional dyspepsia.

Table S1. Baseline features of the inflammatory satus in the gastric mucosa of 248 H. pylori-infected women patients with functional dyspepsia stratified by IL1B -31C/T genotypes. GenotypesP C allele dominance P T allele dominance P CC CT TT CC+CT TT CC CT+TT Corpus Chronic inflammation 0.639 0.377 0.508 Absent / Mild 42 (73.7) 74 (71.2) 58 (66.7) 116 (72.0) 58 (66.7) 42 (73.7) 132 (69.1) Moderate / Severe 15 (26.3) 30 (28.8) 29 (33.3) 45 (28.0) 29 (33.3) 15 (26.3) 59 (30.9) Inflammatory activity 0.201 0.126 0.143 Absent / Mild 50 (87.7) 85 (81.7) 66 (75.9) 135 (83.9) 66 (75.9) 50 (87.7) 151 (79.1) Moderate / Severe 7 (12.3) 19 (18.3) 21 (24.1) 26 (16.1) 21 (24.1) 7 (12.3) 40 (20.9) Incisura Chronic inflammation 0.988 0.885 0.999 Absent / Mild 20 (35.1) 37 (35.6) 30 (34.5) 57 (35.4) 30 (34.5) 20 (35.1) 67 (35.1) Moderate / Severe 37 (64.9) 67 (64.4) 57 (65.5) 104 (64.6) 57 (65.5) 37 (64.9) 124 (64.9) Inflammatory activity* 0.201 0.227 0.467 Absent / Mild 37 (64.9) 78 (75.0) 55 (64.0) 115 (71.4) 55 (64.0) 37 (64.9) 133 (70.0) Moderate / Severe 20 (35.1) 26 (25.0) 31 (36.0) 46 (28.6) 31 (36.0) 20 (35.1) 57 (30.0) Antrum Chronic inflammation 0.036 0.015 0.881 Absent / Mild 17 (29.8) 38 (36.5) 17 (19.5) 55 (34.2) 17 (19.5) 17 (29.8) 55 (28.8) Moderate / Severe 40 (70.2) 66 (63.5) 70 (80.5) 106 (65.8) 70 (80.5) 40 (70.2) 136 (71.2) Inflammatory activity 0.119 0.075 0.809 Absent / Mild 33 (57.9) 69 (66.3) 45 (51.7) 102 (63.4) 45 (51.7) 33 (57.9) 114 (59.7) Moderate / Severe 24 (42.1) 35 (33.7) 42 (48.3) 59 (36.6) 42 (48.3) 24 (42.1) 77 (40.3) * N = 247, data missing for one patient.

ABSTRACT. The aim of this study was to examine the effect of polymorphisms in the cytochrome P450 (CYP) 2C19 gene (CYP2C19) on the Helicobacter pylori eradication rate in Brazilian patients with functional dyspepsia. Adults diagnosed with functional dyspepsia based on the ROME III criteria and infected with H. pylori were recruited to this study. The patients were subjected to gastrointestinal endoscopy and the H. pylori status was defined when both urease test and histopathology results were negative or positive. The patients were treated with proton pump inhibitor-based triple therapy (omeprazole, amoxicillin, and clarithromycin). CYP2C19*2 and CYP2C19*3 were genotyped by polymerase chain reaction-restriction fragment length polymorphism. One hundred and forty-eight patients (81.8% women) with a mean (± SD) age of 46.1 (12.2) years were included in this study. Based on the CYP2C19 genotypes, the patients were classified as homozygous extensive metabolizer (HomEM; 67.6%), heterozygous extensive metabolizer (HetEM; 26.3%), or poor metabolizer (PM; 6.1%). The H. pylori eradication rates in patients with HomEM, HetEM, and PM were 85.0, 89.7, and 100.0% (P = 0.376), respectively. The included study population comprised a high frequency of patients carrying the HomEM genotype. Although the genotypes of CYP2C19 variants were not statistically significant, the results of this study suggest a possible effect of the PM genotype on the efficacy of H. pylori eradication.