RESUMO
BACKGROUND: Coronary artery disease (CAD) is a multifactorial disease that may be caused by the interaction between environmental and genetic risk factors. Glutathione S-transferases (GSTs) are known to participate in detoxification and metabolism of a wide range of xenobiotic compounds and oxidative stress products. Considering the interaction between environmental and genetic factors in CAD, we investigated the genetic polymorphisms of GSTM1, GSTT1, and GSTP1 in the Iranian population. PATIENTS AND METHODS: Two hundred and forty-four CAD cases and 281 healthy controls were studied. The genotype of GSTM1, GSTT1, and GSTP1 genes was determined by multiplex polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP) techniques. Multivariable logistic regression analysis was used to calculate the odds ratios (ORs) and 95% confidence intervals (CI). Multifactor dimensionality reduction (MDR) analysis was also carried out to analyze the gene-gene and gene-environment interaction. RESULTS: The genotype and allele distribution of the three variations were not significantly different between CAD patients and controls (p > 0.05). The subgroup analysis revealed no significant gene-gene interactions or gene-gene combination effects linked to CAD susceptibility. However, MDR analysis selected the GSTM, GSTT pairwise and three genes combination models associated with the susceptibility to CAD. In addition, its result revealed that smoking in combination with GSTM1 (two-way) and GSTT, GSTP (three-way) genes might increase the risk of CAD. Furthermore, a significant interaction between GSTT1-null polymorphism and dyslipidemia was found in multivariable logistic regression analyses in the gene-environmental interactions on CAD risk. CONCLUSION: Our results suggest that the GSTM1, GSTT1 and GSTP1 genetic variations are not directly associated with the susceptibility to CAD in Iranian patients. Due to MDR results, there might be a non-linear association between interactions of two or three genes and smoking with CAD. There is also an association between CAD risk factors and GST variations, which requires supplementary confirmation with larger sample sizes.
RESUMO
Single nucleotide polymorphisms (SNPs) in a number of genes involved in sperm maturation are considered as one of the main factors for male infertility. The aim of the present case-control study was to examine the association of SNPs in protamine1 (PRM1) and protamine2 (PRM2) genes with idiopathic teratozoospermia. In this case-control study, some SNPs in PRM1 (c.49 C>T, c.102 G>T and c.230A>C) and PRM2 (rs545828790, rs115686767, rs201933708, rs2070923 and rs1646022) were investigated in 30 idiopathic infertile men with teratozoospermia (case group) in comparison with 35 fertile men (controls). Genotyping of SNPs was undertaken using polymerase chain reaction (PCR)-direct sequencing. For PRM1, c.230A>C, as a synonymous polymorphism, was detected in both teratozoospermic men (heterozygous n=26, homozygous minor n=1) allele frequency C(48) A(52) and controls (heterozygous n=15, homozygous minor n=4). All cases and controls were genotyped for rs545828790 in PRM2, a missense polymorphism, as well as rs115686767 and rs201933708, both of which synonymous variants. The findings showed an intronic variant in PRM2 (rs2070923) was also present in both groups. Also, rs1646022, a missense polymorphism, occurred in teratozoospermic men (heterozygous n=10, homozygous minor n=5) and controls (heterozygous n=13, homozygous minor n=2). However, there were no significant differences in SNPs of PRM1 and PRM2 between the two groups, however, for c.230A>C, the frequency of the CA genotype was significantly higher in infertile men with teratozoospermia (P=0.001). We demonstrate that PRM2 G398C and A473C polymorphisms were associated with the teratozoospermia and its genetic variation was in relation to semen quality, sperm apoptosis, and morphology in the Iranian population. This study is a preliminary study and presenting data as part of a future comprehensive study to clinically establish whether these gene polymorphisms are biomarkers for susceptibility to teratozoospermia.
RESUMO
BACKGROUND: Asthenozoospermia is one of the etiologies for male factor infertility. It was shown that any abnormality in protamines genes, reduction of protamines transcript and protamines deficiency may play a key role in asthenozoospermia. OBJECTIVE: The aim of the current study was the evaluation of protamine-1 and 2 genes (PRM1 and PRM2) polymorphisms in asthenozoospermic men. MATERIALS AND METHODS: In this case-control study, the samples were corresponded to asthenozoospermic specimens of infertile men. The normozoospermic samples were considered as the control group. DNA sequence amplification was performed using four PRM1 and PRM2 primers, designed from 5' to 3' flank regions. The human PRM1 and PRM2 gene sequences were screened in search of potential mutations in highly prevalent polymorphism regions in asthenozoospermia versus normozoospermia. RESULTS: Totally, nine highly prevalent polymorphism regions between the forward and reverse primers were screened. Three of them corresponded to PRM1 and six to PRM2. The most prevalent polymorphism regions in PRM1 were related to 102G>T (rs35576928), 49C>T (rs140477029) and 139C>A (rs737008). In the PRM2, 6 highly prevalent polymorphisms regions were screened, including 248C>T (rs779337774), 401G>A (rs545828790), 288C>T (rs115686767), 288G>C (rs201933708), 373C>A (rs2070923), and 298G>C (rs1646022). The allele frequencies of three upper mentioned single nucleotide polymorphisms in asthenozoospermic men including 373C>A, 298G>C and 139C>A was higher than the control group. CONCLUSION: Our findings indicated that the frequency of some altered genotypes in asthenozospermia was slightly higher than control group. We proposed more extensive studies to be sure that; these genotypes can precisely be related to diagnosis of asthenozoospermia, as the molecular markers.
RESUMO
BACKGROUND: Endometriosis is a disease that affects women of reproductive age. This disease is characterized by the presence of endometrial-like tissues (endometrial or stromal glands) outside the uterus and shows significantly elevated prevalence in industrial regions. Additionally, an interaction between genetics and environmental factors is assumed for the disease. Enzymes belonging to the cytochrome P450 (CYP) family are participated in detoxiï¬cation process of a wide range of environmental toxins and carcinogens. Thereby, they are good link for the interaction. CYP1A1 which belong to cytochrome P450 (CYPs) superfamily, is a very important gene for the metabolism of carcinogens. OBJECTIVE: The aim of this study was to analyze the frequency of the MspI polymorphism of CYP1A1 gene and its relation to endometriosis. MATERIALS AND METHODS: Genomic DNA was isolated from 93 endometriosis women and 139 healthy controls. Genotyping was performed using polymerase chain reaction followed by restriction fragment length polymorphism analysis. RESULTS: Frequencies of the TT, TC, and CC genotype of CYP1A1 gene polymorphism in patients were 73.1%, 22.6%, and 4.3%, while frequencies in controls were 74.1%, 22.3%, and 3.6%, respectively. So there was no significant differences between the genotypes in two groups (p=0.961). CONCLUSION: According to our study, MspI polymorphism of CYP1A1 gene appears to be not associated with the risk of endometriosis in the studied population. However, additional studies, especially with larger sample size are needed to validate these findings.
