Two novel SNPs in ATXN3 3' UTR may decrease age at onset of SCA3/MJD in Chinese patients

Spinocerebellar ataxia type 3 (SCA3), or Machado-Joseph disease (MJD), is an autosomal dominantly-inherited disease that produces progressive problems with movement. It is caused by the expansion of an area of CAG repeats in a coding region of ATXN3. The number of repeats is inversely associated wit...

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Bibliographic Details
Published in:PloS one 2015-02, Vol.10 (2), p.e0117488-e0117488
Main Authors: Long, Zhe, Chen, Zhao, Wang, Chunrong, Huang, Fengzhen, Peng, Huirong, Hou, Xuan, Ding, Dongxue, Ye, Wei, Wang, Junling, Pan, Qian, Li, Jiada, Xia, Kun, Tang, Beisha, Ashizawa, Tetsuo, Jiang, Hong
Format: Article
Language:English
Subjects:
3' Untranslated Regions
Adolescent
Adult
Age
Age of Onset
Aged
Alleles
Asian Continental Ancestry Group - genetics
Ataxia
Ataxin-3 - genetics
China
Deoxyribonucleic acid
DNA
Female
Gene Frequency
Genes
Genetics
Genotype
Genotypes
Hospitals
Humans
Laboratories
Machado-Joseph disease
Machado-Joseph Disease - genetics
Male
Middle Aged
Mutation
Neurology
Patients
Polyglutamine
Polymorphism, Single Nucleotide
Single nucleotide polymorphisms
Single-nucleotide polymorphism
Trinucleotide repeats
Young Adult
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Summary:Spinocerebellar ataxia type 3 (SCA3), or Machado-Joseph disease (MJD), is an autosomal dominantly-inherited disease that produces progressive problems with movement. It is caused by the expansion of an area of CAG repeats in a coding region of ATXN3. The number of repeats is inversely associated with age at disease onset (AO) and is significantly associated with disease severity; however, the degree of CAG expansion only explains 50 to 70% of variance in AO. We tested two SNPs, rs709930 and rs910369, in the 3' UTR of ATXN3 gene for association with SCA3/MJD risk and with SCA3/MJD AO in an independent cohort of 170 patients with SCA3/MJD and 200 healthy controls from mainland China. rs709930 genotype frequencies were statistically significantly different between patients and controls (p = 0.001, α = 0.05). SCA3/MJD patients carrying the rs709930 A allele and rs910369 T allele experienced an earlier onset, with a decrease in AO of approximately 2 to 4 years. The two novel SNPs found in this study might be genetic modifiers for AO in SCA3/MJD.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0117488