Genetic analysis of the FBXO42 gene in Chinese Han patients with Parkinson's disease.
BACKGROUND
Parkinson's disease (PD), the second most common neurodegenerative disease, is characterized by loss of dopaminergic neurons in the substantia nigra. The clinical manifestations of PD encompass a variety of motor and non-motor symptoms. Mutations in the F-box protein 7 gene (FBXO7) have been identified to cause Parkinsonian-pyramidal syndrome, an autosomal recessive form of Parkinsonism. The F-box protein 42 gene (FBXO42), a paralog of the FBXO7 gene, is involved in the ubiquitin-proteasome system that may play a role in the pathogenesis of PD.


METHODS
To determine whether the FBXO42 gene is associated with PD, we performed a systematic genetic analysis of the FBXO42 gene in 316 PD patients and 295 gender-, age-, and ethnicity-matched normal controls.


RESULTS
We identified a novel variant c.1407T>C (p.S469S) and three known single nucleotide variants, including rs2273311, rs12069239 and rs35196193 in the FBXO42 gene in PD patient group. None of the three known variants displayed statistically significant difference in either genotypic or allelic distributions between patient and control groups (all P > 0.05). Haplotype analysis showed that a common haplotype (G-C-G) for the three single nucleotide variants conferred a 1.69-fold increased risk for PD (P = 0.008 after Bonferroni correction, OR = 1.69, 95% CI = 1.06-2.71).


CONCLUSIONS
Our findings suggest that a haplotype of the FBXO42 gene might be associated with a higher susceptibility to PD.
Center for Experimental Medicine, the Third Xiangya Hospital, Central South University, 138 Tongzipo Road, Changsha, Hunan 410013, China. hdeng008@yahoo.com.
Kai
K
Gao
Xiong
X
Deng
Wen
W
Zheng
Zhi
Z
Song
Anding
A
Zhu
Xiaofei
X
Xiu
Hao
H
Deng
D000368:Aged; D044466:Asian People / Q000208:ethnology / Q000235:genetics; D044783:F-Box Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000208:ethnology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
D044783:F-Box Proteins