Objective: To investigate the contribution of mitochondrial DNA (mtDNA) haplogroups to the age at onset (AO) of Spinocerebellar Ataxia type 2 (SCA2) in Indian patients, independent of the CAG repeat length.

Background: Spinocerebellar Ataxia type 2 (SCA2) is an autosomal dominant polyglutamine ataxia caused by an expanded CAG repeat in the ATXN2 gene. Mitochondrial DNA (mtDNA) haplogroups have been suggested as potential disease modifiers in polyglutamine disorders.

Method: To investigate if mtDNA haplogroups contribute to age at onset (AO) in SCA2, we sequenced the D-LOOP and hypervariable regions of the mitochondrial genome in mixed Indian populations. SCA2 patients displayed expanded CAG repeat sizes.

Results: The major haplogroups identified in SCA2 patients were H (24.9%), L (6.5%), U (17.1%), W (1.8%), M (24.9%), G (0.5%), A (2.3%), N (6.0%), J (0.9%), I (1.4%), T (2.8%), R (3.2%), D (0.9%), C (0.5%), K (0.9%), P (3.2%), and S (2.3%). Age at onset significantly differed among patients with the same expanded CAG repeat size. ANCOVA analysis revealed that mtDNA haplogroups significantly affect AO (p = 0.005), with haplogroups M and T showing the most significant associations.

Conclusion: This study shows that mtDNA haplogroups influence AO in SCA2 patients independently of CAG repeat length. Haplogroups M and T were particularly associated with variations in AO. Further research is needed to investigate the mechanisms behind these associations and validate the findings in larger cohorts.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/the-role-of-mitochondrial-dna-haplogroups-in-determining-the-age-of-onset-in-indian-sca2-patients/