Mitochondrial complex i gene variations; As a potential genetic risk factor in pathogenesis of multiple sclerosis

© 2014 Elsevier B.V. Background and purpose:Multiple sclerosis (MS) is an autoimmune-mediated inflammatory and debilitating disease of the central nervous system. Several investigations have suggested that the mitochondrial DNA encoded subunits of complex I gene variations are involved in the progression of MS. In this study, we investigated the possible association between mitochondrial complex I gene variations and MS in a Filipino population. Material and methods: A total of 300 individuals were included in the present study, two-hundred patients with MSclinical symptoms, and one-hundred healthy subjectswithoutMS clinical features.Weamplified target genes of mtDNA using polymerase chain reaction technique (PCR), and sequenced these to evaluate mitochondrial complex I gene variations. Results:We found nine variations (Nt 4216 T N C, Nt 5153 A N G, Nt 10142 C N T, Nt 11353 T N C, Nt 11935 T N C, Nt 12062 C N T, Nt 13042 G N A, Nt 13708 G N A and Nt 14179 G N A) in mtDNA-encoded complex I subunit genes. Our results showed that the prevalence of ND1, ND2, ND3, ND4 and ND5 gene variationswas significantly higher in patients than in healthy controls (P b 0.0001).Whereas, the frequency of Nt 14179 G N A variation inND6 gene was significantly higher in the control group compared with the patients (P b 0.0001). Conclusion: Taken together our data supports a strongly positive association between mitochondrial complex I gene variations and MS pathogenesis in a Filipino population

Investigation of Exportin 5 (XPO5) mRNA expression in breast cancer patients

Background and objectives: Deregulation in the expression of microRNAs is involved in the pathogenesis of various malignancies. Impaired microRNAs processing pathway is one possible mechanism for global deregulation of the miRNAs. Exportin 5 (XPO5) is a key member of this pathway that links nuclear and cytoplasmic steps of miRNAs biogenesis together. XPO5 deregulation has been reported in some cancers but very little is known about its role in breast cancer. Therefore, this study aimed to evaluate the mRNA expression of XPO5 in breast cancer in an Iranian population. Methods: In this case-control study, 30 tumoral tissues and 30 tumor-free margins were collected from breast cancer patients. After RNA extraction and cDNA synthesis, XPO5 mRNA expression level was assessed using quantitative Real-Time PCR. Results: Our results showed that XPO5 was overexpressed in 53.3% of tumoral tissues but the difference in the gene expression level between tumoral tissues and tumor-free margins was not statistically significant (P-value=0.834). XPO5 expression level showed no statistically significant correlation and association with clinical and pathological parameters. Conclusion: Overexpression of XPO5 in large percent of patients indicates that high level of XPO5 expression may be a tumorigenic factor for breast cancer which needs to be investigated more deeply

The expression of Drosha, DGCR8, Dicer and Ago-2 genes are upregulated in human umbilical vein endothelial cells under hyperglycemic condition

Objectives. It has been shown that dysregulation of miRNAs expression contributes to the pathogenesis and progression of the diabetes and diabetes-related complications. Drosha, DGCR8, Dicer, and Ago-2 are involved in the miRNA maturation. The aim of the present study was to investigate the mRNA expression levels of these genes in the human umbilical vein endothelial cells (HUVECs) under hyperglycemic condition

Diverse pattern of gap junction beta-2 and gap junction beta-4 genes mutations and lack of contribution of DFNB21, DFNB24, DFNB29, and DFNB42 loci in autosomal recessive nonsyndromic hearing loss patients in Hormozgan, Iran

Background: We aimed to determine the contribution of four DFNB loci and mutation analysis of gap junction beta-2 (GJB2) and GJB4 genes in autosomal recessive nonsyndromic hearing loss (ARNSHL) in South of Iran. Materials and Methods: A total of 36 large ARNSHL pedigrees with at least two affected subjects were enrolled in the current study. The GJB2 and GJB4 genes mutations were screened using direct sequencing method. The GJB2 and GJB4 negative families were analyzed for the linkage to DFNB21, DFNB24, DFNB29, and DFNB42 loci by genotyping the corresponding STR markers using polymerase chain reaction-PAGE method. Results: We found a homozygous nonsense mutation W77X and a homozygous missense mutation C169W in 5.55% of studied families in GJB2 and GJB4 genes, respectively. Five heterozygous mutations including V63G, A78T, and R127H in GJB2 gene, and R103C and R227W in GJB4 gene were detected. We identified two novel variations V63G in GJB2 and R227W in GJB4. In silico analysis predicted that both novel variations are deleterious mutations. We did not unveil any linkage between DFNB21, DFNB24, DFNB29, and DFNB42 loci and ARNSHL among studied families. Conclusion: This is the first report of GJB2 and GJB4 mutations from Hormozgan population. According to the previous publications regarding GJB2 and GJB4 mutations, the distribution of the mutations is different from other parts of Iran that should be considered in primary health-care programs. Further investigations are needed to evaluate the contribution of other loci in ARNSHL subjects in South of Iran

Prevalence of thrombophilic gene polymorphisms in an Azari population of Iran

There is several evidence suggests that thrombophilic gene polymorphisms may influence susceptibility to thromboembolic events. The prevalence of these polymorphisms is different in various races and ethnics. Accordingly, we studied the prevalence of Factor V (G1691A and A4070G), prothrombin G20210A and PAI-1 4G/5G in healthy northwest population of Iran. In this prospective study, 500 healthy individuals, who had no history of both personal and family history of thromboembolic disorders, were selected as a sample of healthy population in northwestern Iran. Genotyping of these polymorphisms was performed using the amplification refractory mutation system-polymerase chain reaction method. No significant differences were detected between the expected and observed frequencies of FV G1691A and A4070G, prothrombin G20210A polymorphisms (P>0.05), while the expected frequency of 4G allele was significantly more than observed frequency in the studied population (P<0.01). These findings were compared with other reports from various populations. In conclusion, the allele frequency for FV G1691A and PAI-1 4G/5G polymorphisms showed relative consistency compared to those of previous studies, while the incidence pattern of FV A4070G polymorphism in Northwestern population of Iran showed conflicting results regarding other studied population. The prothrombin G20210A polymorphism was observed at a higher frequency than other studied populations

Variations of Serum Leptin and Resistin levels in Healthy non- Diabetic women with different degrees of Obesity

ABSTRACT The role of leptin and resistin serum concentrations in pathogenesis of obesity is considered an emerging topic issue in clinical biochemistry researches. This study was carried out to evaluate the variation of leptin and resistin serum levels in women with different grades of obesity. A total of 149 non-diabetic women were included in this study Adipose tissue is an endocrine organ that secretes a wide variety of proteins which contribute to regulation of body weigh