Polymorphisms in proinflammatory cytokines genes and susceptibility to Multiple Sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disorder of the central nervous system (CNS). It is immunologically induced in genetically susceptible individuals. Proinflammatory cytokines play an important role as genetic polymorphisms in their genes might be involved in the susceptibility and pathogenesis of MS. OBJECTIVE: In this study, our goal was to analyze the association between the gene polymorphisms in interleukin-16 (IL-16) (rs4072111 C/T), tumor necrosis factor-α (TNF-α) -308 G/A (rs1800629 G/A) and IL-18 -607 C/A (rs1946518 C/A) and the susceptibility and clinical features of MS in an Egyptian cohort. METHODS: We genotyped these genetic polymorphisms in 150 subjects including 93 patients with MS and 57 unrelated healthy subjects. We employed polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) method for determining the IL-16 (rs4072111 C/T) and TNF-α -308 G/A (rs1800629 G/A) polymorphisms, and the allele- specific polymerase chain reaction (AS-PCR) method for IL-18-607 C/A (rs1946518 C/A) polymorphism. RESULTS: The IL-16 (rs4072111 C/T) polymorphism was not polymorphic in both MS patients and the healthy volunteers. For the TNF-α-308 G/A (rs1800629 G/A) polymorphism, the mutant AA genotype and A allele are not associated with the susceptibility of MS, however, associated with the severity and disability progression of the disease. We observed a statistically significant increase in the mean values of Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Severity Score (MSSS) in patients with AA genotype and A allele compared with those of genotypes GG and GA, and the G allele, and regression analysis confirmed that this polymorphism is a predictor of disease disability using EDSS. For the IL-18 -607 C/A (rs1946518 C/A) polymorphism, the frequency of mutant AA genotype and A allele showed significant differences between the MS patients and healthy controls. CONCLUSION: The TNF-α-308 AA genotype and A allele could be related to disability progression and severity of MS and the IL-18-607 AA genotype A allele could be related to susceptibility of the disease in the Egyptian cohort.

Novel mutations in the displacement loop of mitochondrial DNA are associated with acute lymphoblastic leukemia: a genetic sequencing study.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common cancer diagnosed in children and represents approximately 25% of cancer diagnoses among those younger than 15 years of age. MATERIALS AND METHODS: This study investigated alterations in the displacement loop (d-loop) region of mitochondrial DNA (mtDNA) as a risk factor and diagnostic biomarker for early detection and diagnosis of acute lymphoblastic leukemia. Using mtDNA from 23 subjects diagnosed with acute lymphoblastic leukemia, the first 450 bp of the d-loop region were amplified and successfully sequenced. RESULTS: This revealed 132 mutations at 25 positions in this region, with a mean of 6 alterations per subject. The d-loop alterations in mtDNA in subjects were all identified as single nucleotide polymorphisms in a homoplasmic distribution pattern. Mutant alleles were observed in all subjects with individual frequency rates of up to 95%. Thirteen mutant alleles in the d-loop region of mtDNA occurred with a high frequency. Novel alleles and locations were also identified in the d-loop of mtDNA as follows: 89 G insertions (40%), 95 G insertions (13%), 182 C/T substitutions (5%), 308 C insertions (19%), and 311 C insertions (80%). The findings of this study need to be replicated to be confirmed. CONCLUSIONS: Further investigation of the relationship between mutations in mitochondrial d-loop genes and incidence of acute lymphoblastic leukemia is recommended.