Objective: Assessing the role of LIG1 Exon 6 A→C polymorphism acting as a modifier of clinical severity in patients with Spinocerebellar ataxia type 2 (SCA2).

Background: SCA2 shows huge clinical variability even in individuals sharing the same CAG repeat length. Additional genetic modifiers have been proposed to explain clinical variability in SCA2.

Method: A case-control study involving 205 Cuban SCA2 patients and 105 control individuals was conducted. The ATXN2 CAG-repeat length was determined by PCR followed by polyacrylamide gel electrophoresis, while the Exon 6 A→C was assessed by PCR/RFLP. The age at disease onset and the SARA score were used as clinical outcome variables.

Results: The “C” variant was most frequently observed in both, patients and local control individuals, accounting for 52.74 percent of the total. The LIG1 Exon 6 A→C genotypes were in Hardy-Weinberg equilibrium in both study groups, patients (²=2.37; p=0.123) and control individuals (²=0.48; p=0.489). No significant associations were found between SCA2 and LIG1 Exon 6 A→C alleles or genotypes. Regression analysis showed that LIG1 Exon 6 A→C genotypes contributed in a 1.9 percent to explain age at onset variability (p=0.006). The occurrence of at least one “C” allele produced an average age at onset 4.34 years earlier than the “AA” genotype. The LIG1 Exon 6 A→C genotypes showed no significant effects on SARA score under any of the genetic models examined.

Conclusion: Evidence for a modifier effect of the LIG1 Exon 6 A→C polymorphism on the age at disease onset of patients with Spinocerebellar ataxia type 2 is provided, suggesting that DNA repair pathways might be relevant to SCA2 physiopathology.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/lig1-polymorphism-modifies-the-age-at-onset-in-patients-with-spinocerebellar-ataxia-type-2/