Lack of association between mitochondrial DNA G15257A and G15812A variations and multiple sclerosis
Sasan Andalib1, Mahnaz Talebi1, Ebrahim Sakhinia2
1Neurosciences Research Center, Imam Reza Hospital, Tabriz University of Medical Sciences, Tabriz, Iran.
Background:
Multiple sclerosis (MS) is a debilitating disease of the central nervous system for which no definitive therapy has yet been developed. The etiology remains uncertain, but there is evidence of genetic susceptibility to the disease, including contributions from mitochondrial DNA (mtDNA) variations to the pathogenesis of MS. G15257A and G15812A are variations of the mtDNA tRNA(Thr) gene in MS sufferers of different populations. The present study tested the hypothesis of an association of the G15257A and G15812A variations of the mtDNA tRNA(Thr) gene to the susceptibility to MS in an Iranian population.
Material And Methods:
Two hundred subjects included 100 MS patients and 100 unrelated healthy controls. DNA was extracted from blood samples by means of a salting-out method. The mtDNA fragment was amplified by polymerase chain reaction (PCR). Restriction fragment length polymorphism (RFLP) analysis was done by digestion of the PCR products with Acc I and Rsa I restriction endonuclease enzymes for mtDNA G15257A and G15812A variations, respectively. Afterwards, the restriction products were visualized by electrophoresis using 3% Agarose gel and safe DNA gel staining. To confirm the accuracy of genotyping procedure, sequencing of the mtDNA fragments was carried out in randomly selected samples.
Results:
The mtDNA G15257A variation was found in one of the 100 patients and one of the 100 controls (P=0.637) (odds ratio [OR]=1, 95% confidence interval [95% CI]=0.0-79.2). The mtDNA G15812A variation was not found in any of the 100 patients or 100 controls (0%) (P=1) (OR=1, 95% CI=0.0-79.2).
Conclusion:
The evidence from the present study is inconsistent with the hypothesis that the G15257A and G15812A variations in the mtDNA tRNA(Thr) gene are associated with susceptibility to MS in the selected population.
Insights
This study investigated mitochondrial DNA variations (G15257A and G15812A) in the tRNA(Thr) gene for multiple sclerosis (MS) susceptibility in an Iranian population. No significant association was found between these mtDNA variations and MS risk.
Area of Science:
- Genetics
- Neurology
- Mitochondrial Biology
Background:
- Multiple sclerosis (MS) is a central nervous system disease with uncertain etiology.
- Genetic factors, including mitochondrial DNA (mtDNA) variations, are implicated in MS pathogenesis.
- Specific mtDNA variations (G15257A and G15812A) in the tRNA(Thr) gene have been observed in MS patients globally.
Purpose of the Study:
- To test the hypothesis that mtDNA G15257A and G15812A variations are associated with MS susceptibility in an Iranian population.
- To investigate the role of specific mitochondrial genetic markers in the development of multiple sclerosis.
Main Methods:
- Case-control study involving 100 MS patients and 100 healthy controls from Iran.
- DNA extraction from blood samples followed by polymerase chain reaction (PCR) amplification of the target mtDNA region.
- Restriction fragment length polymorphism (RFLP) analysis using Acc I and Rsa I enzymes to detect G15257A and G15812A variations, respectively.
- Sequencing of randomly selected samples for genotyping accuracy confirmation.
Main Results:
- The mtDNA G15257A variation was detected in one patient and one control, showing no statistically significant association with MS (P=0.637).
- The mtDNA G15812A variation was absent in both MS patients and controls (0%), indicating no association with MS risk (P=1).
- Odds ratios for both variations were 1, with wide confidence intervals, suggesting a lack of effect.
Conclusions:
- The findings do not support an association between the mtDNA G15257A and G15812A variations and susceptibility to multiple sclerosis in the studied Iranian population.
- Further research may be needed to explore other mtDNA variations or genetic factors in MS pathogenesis within this demographic.
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