Polymorphisms in DNA methylation–related genes are linked to the phenotype of Machado-Joseph disease

Dongxue Ding, Chunrong Wang, Zhao Chen, Huirong Peng, Kai Li, Xin Zhou, Yun Peng, Puzhi Wang, Xiaocan Hou, Tianjiao Li, Rong Qiu, Kun Xia, Jorge Sequeiros, Tetsuo Ashizawa, Beisha Tang, Hong Jiang

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


DNA methylation has been reported as an important regulator of genomic structure stability, including large tandem repeats. To test the modulation effect of variants in DNA methylation–related genes on distribution of expanded (CAG)n alleles and age at onset (AO) of patients with Machado-Joseph disease (MJD), we conducted an association analysis on 23 selected SNPs in these genes in 613 patients with MJD and 581 controls. There were significant differences in the distribution of rs12957023 between patients and controls (OR = 1.296, p = 0.007 and OR = 1.206, p = 0.008, for genotype and alleles, respectively). The distribution of (CAG)n size was also different between patients carrying a CC and the other genotypes (TT and TC, p = 0.011 for expanded (CAG)n and p = 0.012 for normal size alleles), indicating that DNA methylation might modulate the (CAG)n instability. We found also that rs13420827 in DNMT3A and rs7354779 in DNMT3L contribute to AO of MJD (p = 0.019 and p = 0.008, respectively). In conclusion, our data provide the first evidence that SNPs in DNA methylation–related genes may contribute to (CAG)n instability and modulate the AO of this disease.

Original languageEnglish (US)
Pages (from-to)225.e1-225.e8
JournalNeurobiology of Aging
StatePublished - Mar 2019


  • ATXN3
  • Age at onset
  • DNA methylation
  • Epigenetic regulation
  • MJD
  • SCA3

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Developmental Biology
  • Clinical Neurology
  • Geriatrics and Gerontology


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