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

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