Investigating the association of matrix metalloproteinase-2 gene variants with endometriosis in an Iranian population.

OBJECTIVES: matrix metalloproteinases including matrix metalloproteinase-2 play a key role in endometrial extra cellular matrix breakdown in endometriosis. Aberrant expression of matrix metalloproteinase-2 has been reported in eutopic and ectopic endometrial tissue of endometriosis patients so altered expression of matrix metalloproteinase-2 due to polymorphisms may lead to establishment and progression of endometriosis. In this study the association between -735 C/T (rs2285053) and -1575 G/A (rs243866) variants of matrix metalloproteinase-2 gene with presence of endometriosis in an Iranian population were investigated for the first time. STUDY DESIGN: A case-control association study was conducted to investigate the role of MMP-2-735 C/T and _1575 G/A variants in development of endometriosis. Polymerase chain reaction-restriction fragment length polymorphism method was used to determine genotype frequencies of these variants in 100 endometriosis patients and 200 normal samples. Total genomic DNA was extracted from blood samples and single-nucleotide polymorphism flanking regions were amplified using designed specific primers. Enzymatic digestion was performed using Pag I and Hinf I restriction enzymes for rs2285053 and rs243866 variants, respectively. Statistical analysis was ascertained using statistical package for social science version 16 and "SHEsis" software. RESULTS: There were no significant differences in genotype frequencies of rs2285035 (-735C/T) variant between case and control groups (CC + CT vs. TT p = 0.40; OR = 0.50, 95 % CI 0.100-2.551). There were also no significant differences for C allele frequencies in both case and control groups (p = 0.9). For variant rs243866 (-1575 G/A) the differences in genotype frequencies between case and controls group were determined to be significant (GG + GA vs. AA p = 0.041; OR = 6.46, 95 % CI 0.82-50.43). The frequency of G allele was significantly different in case and control groups (p = 0.037). CONCLUSION: In conclusion, existence of rs243866 variant in promoter region of matrix metalloproteinase-2 gene can increase the risk of endometriosis in Iranian women.

MIF 173 G>C variation was associated with depressive disorder in type 2 diabetes in an Iranian population.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a continuous metabolic disease linked with increased rate of mortality and morbidity. High levels of glucose can damage organs including kidneys, eyes, and the nervous system. Individuals with T2DM have a high prevalence of major depression. One possible question we aimed to address was the extent of co-occurrence of diabetes and depression resulting from correlated genetic risk factors. OBJECTIVES: The current study aimed to investigate the possible associations between the macrophage migration inhibitory factor (MIF) functional variant and the risk of developing depression in T2DM patients. PATIENTS AND METHODS: The study groups consisted of 120 patients with T2DM and comorbid depression and 120 patients with T2DM, without depression, who were recruited from the same region. Genotyping of the MIF -173 G > C (rs755622) variant was performed using Polymerase Chain Reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP). In addition, the level of MIF expression was comparatively evaluated in both groups by quantitative real-time PCR. RESULT: The data showed that the presence of C allele (GC + CC vs. GG) might predispose females to depression in patients with T2DM. In addition, patients with T2DM carrying at least one C allele showed significantly elevated levels of MIF RNA expression in comparison to individuals with GG genotype. CONCLUSION: MIF variant could be considered as a factor making female patients with T2DM vulnerable to depression. So, this might be an important result for precise diagnosis and/or earlier treatment.

MTHFR AND ApoE genetic variants association with sudden sensorineural hearing loss.

HYPOTHESIS: Although the pathogenesis of sudden sensorineural hearing loss (SSNHL) is not clear, however several causes including genetic factors seems to be implicated. We hypothesized that common genetic variants might be involved in SSNHL. BACKGROUND: SSNHL is known to be an idiopathic disease because the causative factors have not been identified. Several causes including genetic and viral infection besides immune system reaction, neurological disorders, medications, etc. have been previously reported. We examined the association between ApoE and MTHFR gene variants in SSNHL. METHODS: This study includes case-control scheme encompassing a total of 177 individuals, include patients inflicted with SSNHL and healthy subjects as control group. Genotyping of MTHFR and ApoE variants was conducted by PCR - RFLP method. RESULT: Our study showed that MTHFR rs1801133 allele frequency is significantly different between cases and controls. Also genotype distribution of ApoE was significantly different between patients and healthy controls. CONCLUSIONS: MTHFR C677T and ApoE gene variant may be associated with sudden sensorineural hearing loss in an Iranian population.

Association Between the Polymorphism of Glu298Asp in Exon 7 of the eNOS Gene With Foot Ulcer and Oxidative Stress in Adult Patients With Type 2 Diabetes.

OBJECTIVES: Diabetic foot ulcer (DFU) is a common and major manifestation in patients with diabetes. Oxidative stress (OS) plays an important role in diabetic complications, such as DFU. Nitric oxide deficiency contributes to the impairment of diabetic wound healing. The aim of this study was to examine the association between the eNOS Glu298Asp polymorphism and DFU and oxidative stress in patients with type 2 diabetes mellitus in an Iranian population. METHODS: In this case-control study, 123 patients with type 2 diabetes and DFU and 134 patients without DFU were recruited. The genotypes of eNOS Glu298Asp polymorphism in exon 7 were determined by the polymerase chain reaction-restriction fragment length polymorphism analysis. We measured the levels of thiobarbituric reactive substances and ferric-reducing ability of plasma as the potential markers of OS. RESULTS: There were significant differences in genotype frequencies of eNOS Glu298Asp polymorphism between case and control groups (GG+TG vs. TT; p=0.002; OR=0.22, 95% CI 0.83 to 0.62). Also, the frequency of the T allele in cases was less common than in controls (p=0.004). There was no significant difference in levels of OS parameters and various genotypes (p>0.05). CONCLUSIONS: These results imply that the T allele might be protective against DFU.

Vitamin D receptor gene FokI variant in diabetic foot ulcer and its relation with oxidative stress.

PURPOSE: The patient's suffering and financial costs affiliated with Diabetic Foot Ulcer (DFU), as one of the most important complications of diabetes, are highly undesirable and this highlights the importance of preventive medicine about this disorder. Furthermore hyperglycemia causes generation of free radicals which leads to oxidative stress (OS). Hence, this study aims to examine the association between vitamin D receptor (VDR) gene FokI polymorphism and DFU in Iranian population and also its correlation with OS biomarkers. MATERIALS AND METHODS: In a case-control study, a total of 212 patients with type 2 diabetes with and without diabetic foot ulcer were included. Genotyping was conducted by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis. Samples were analyzed for thiobarbituric reactive substances (TBARS) and ferric reducing ability of plasma (FRAP) as markers of OS. RESULTS: The results indicated a significant difference in genotype frequencies of VDR gene FokI polymorphism in patients with diabetic foot ulcer in comparison to those without diabetic foot ulcer (TT+TC vs. CC p=0.04; OR=1.76; 95% CI=1.02-3.05). Moreover, the patients carrying the T allele had a significantly higher level of TBARS (p=0.01). CONCLUSIONS: We found a significant association between FokI functional variant of VDR gene and diabetic foot ulcer in an Iranian population. Increased levels of TBARS in patients carrying the T allele of FokI polymorphism indicate an association between this variant and OS in patients with diabetes.

A novel deletion and two recurrent substitutions on type VII collagen gene in seven Iranian patients with epidermolysis bullosa.

OBJECTIVES: Epidermolysis bullosa is one of the most important series of mechano-bullous heritable skin disorders which is categorized into four major types according to the layer that bullae forms within basement membrane zone. In dystrophic form of the disease, blisters are made in the sublamina densa zone, at the level of type VII collagen protein which produce anchoring fibrils. Type VII collagen gene is the only responsible gene for this form. The aim of this study was to survey causative mutations of type VII collagen gene among Iranian patients with epidermolysis bullosa. MATERIALS AND METHODS: For this purpose, exons 73-75 were investigated by polymerase chain reaction followed by direct sequencing. RESULTS: In current study, we found three different point mutations in type VII collagen alleles in 7 out of 50 patients. Four patients were homozygous for a new deletion which resulted in frame shift (p.Pro2089fs). Two patients were homozygous for a recurrent glycine substitution (p.G2031S) and one patient was detected with an allele carrying a substitution (p.R2069C). CONCLUSION: The results emphasized heterogeneity in the type VII collagen gene and will provide a sign for early diagnosis and future study of the disease pathogenesis.