title: Two novel SNPs in ATXN3 3' UTR may decrease age at onset of SCA3/MJD in Chinese patients.
abstract: 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.
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P. R. China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Long
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P. R. China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P. R. China; Department of Neurology, Xiangtan Central Hospital, Xiangtan, Hunan 411100, P. R. China.
authors.forename: Chunrong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P. R. China; Department of Neurology & Institute of Translational Medicine at University of South China, the First People's Hospital of Chenzhou, Chenzhou, Hunan 423000, P. R. China.
authors.forename: Fengzhen
authors.initials: F
authors.lastname: Huang
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P. R. China.
authors.forename: Huirong
authors.initials: H
authors.lastname: Peng
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P. R. China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Hou
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P. R. China.
authors.forename: Dongxue
authors.initials: D
authors.lastname: Ding
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P. R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ye
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P. R. China; Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, Hunan 410008, P. R. China; State Key Lab of Medical Genetics, Central South University, Changsha, Hunan 410078, P. R. China.
authors.forename: Junling
authors.initials: J
authors.lastname: Wang
authors.affiliation: State Key Lab of Medical Genetics, Central South University, Changsha, Hunan 410078, P. R. China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Pan
authors.affiliation: State Key Lab of Medical Genetics, Central South University, Changsha, Hunan 410078, P. R. China.
authors.forename: Jiada
authors.initials: J
authors.lastname: Li
authors.affiliation: State Key Lab of Medical Genetics, Central South University, Changsha, Hunan 410078, P. R. China.
authors.forename: Kun
authors.initials: K
authors.lastname: Xia
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P. R. China; Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, Hunan 410008, P. R. China; State Key Lab of Medical Genetics, Central South University, Changsha, Hunan 410078, P. R. China.
authors.forename: Beisha
authors.initials: B
authors.lastname: Tang
authors.affiliation: Department of Neurology, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ashizawa
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P. R. China; Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, Hunan 410008, P. R. China; State Key Lab of Medical Genetics, Central South University, Changsha, Hunan 410078, P. R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
mesh_terms: D020413:3' Untranslated Regions; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics; D000067699:Ataxin-3 / Q000235:genetics*; D002681:China; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D017827:Machado-Joseph Disease / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: D020413:3' Untranslated Regions; D000067699:Ataxin-3