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

doi:10.1016/j.neurobiolaging.2018.11.002

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

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6 Scopus citations

Abstract

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 language	English (US)
Pages (from-to)	225.e1-225.e8
Journal	Neurobiology of Aging
Volume	75
DOIs	https://doi.org/10.1016/j.neurobiolaging.2018.11.002
State	Published - Mar 2019

Keywords

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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10.1016/j.neurobiolaging.2018.11.002

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Ding, D., Wang, C., Chen, Z., Peng, H., Li, K., Zhou, X., Peng, Y., Wang, P., Hou, X., Li, T., Qiu, R., Xia, K., Sequeiros, J., Ashizawa, T., Tang, B., & Jiang, H. (2019). Polymorphisms in DNA methylation–related genes are linked to the phenotype of Machado-Joseph disease. Neurobiology of Aging, 75, 225.e1-225.e8. https://doi.org/10.1016/j.neurobiolaging.2018.11.002

@article{f5e160074a204fd0b0366336af6ea6dc,

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

abstract = "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.",

keywords = "ATXN3, Age at onset, DNA methylation, Epigenetic regulation, MJD, SCA3",

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

note = "Funding Information: This study was supported by the National Key Research and Development Program of China (Nos. 2016YFC0905100 and 2016YFC0901504 to Hong Jiang), the National Natural Science Foundation of China (Nos. 81471156 , 81771231 to Hong Jiang), the Clinical Research Funds of Xiangya Hospital ( 2014L03 to Hong Jiang), the Clinical and rehabilitation fund of Peking University Weiming Biotech Group (No. xywm2015I10 to Hong Jiang) and the National Natural Science Foundation of China (No. 81430023 , 81130021 to Beisha Tang), NIH ( NS083564 to Tetsuo Ashizawa). Publisher Copyright: {\textcopyright} 2018 Elsevier Inc. Copyright: Copyright 2019 Elsevier B.V., All rights reserved.",

year = "2019",

month = mar,

doi = "10.1016/j.neurobiolaging.2018.11.002",

language = "English (US)",

volume = "75",

pages = "225.e1--225.e8",

journal = "Neurobiology of Aging",

issn = "0197-4580",

publisher = "Elsevier",

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TY - JOUR

T1 - Polymorphisms in DNA methylation–related genes are linked to the phenotype of Machado-Joseph disease

AU - Ding, Dongxue

AU - Wang, Chunrong

AU - Chen, Zhao

AU - Peng, Huirong

AU - Li, Kai

AU - Zhou, Xin

AU - Peng, Yun

AU - Wang, Puzhi

AU - Hou, Xiaocan

AU - Li, Tianjiao

AU - Qiu, Rong

AU - Xia, Kun

AU - Sequeiros, Jorge

AU - Ashizawa, Tetsuo

AU - Tang, Beisha

AU - Jiang, Hong

N1 - Funding Information: This study was supported by the National Key Research and Development Program of China (Nos. 2016YFC0905100 and 2016YFC0901504 to Hong Jiang), the National Natural Science Foundation of China (Nos. 81471156 , 81771231 to Hong Jiang), the Clinical Research Funds of Xiangya Hospital ( 2014L03 to Hong Jiang), the Clinical and rehabilitation fund of Peking University Weiming Biotech Group (No. xywm2015I10 to Hong Jiang) and the National Natural Science Foundation of China (No. 81430023 , 81130021 to Beisha Tang), NIH ( NS083564 to Tetsuo Ashizawa). Publisher Copyright: © 2018 Elsevier Inc. Copyright: Copyright 2019 Elsevier B.V., All rights reserved.

PY - 2019/3

Y1 - 2019/3

N2 - 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.

AB - 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.

KW - ATXN3

KW - Age at onset

KW - DNA methylation

KW - Epigenetic regulation

KW - MJD

KW - SCA3

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U2 - 10.1016/j.neurobiolaging.2018.11.002

DO - 10.1016/j.neurobiolaging.2018.11.002

M3 - Article

C2 - 30554804

AN - SCOPUS:85058216488

SN - 0197-4580

VL - 75

SP - 225.e1-225.e8

JO - Neurobiology of Aging

JF - Neurobiology of Aging

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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