Genetic Association Study Of The ATP1B4Gene And The FBXO42Gene In Chinese Han Patients With Parkinson’s Disease

Objective:Systematic analysis of all the coding region in the ATPase Na+/K+transporting beta4polypeptide gene(ATP1B4) was performed to determine whether mutations in the ATP1B4gene are associated with Parkinson’s disease (PD) in a Chinese Han population.Methods:All the coding region and intron/exon boundaries of the ATP1B4gene of100PD patients were analyzed using polymerase chain reaction-single strand conformation polymorphism and sequencing, and the genotype and allele frequency distributions between enlarged PD cohort (202cases and400matched controls) were evaluated by statistical analysis.Results:A single nucleotide variant (c.143T>C, rs2072452) in the ATP1B4gene was identified in our first100PD patients, and this variant was predicted to lead to an amino acid change from valine to alanine at amino acid position48(p.V48A). Given that the ATP1B4gene is located on chromosome X, we stratified the PD cohort into man and woman group for further analysis. Statistical analysis found that no significant difference in either genotypic distribution or allelic distribution between100female cases and200female control subjects (χ2=0.898, P=0.638for genotypic distribution;χ2=0.165, P=0.685for allelic distribution); and the allelic distribution also showed no significant difference between102male cases and200male controls (χ2=1.062, P=0.303).Conclusions:The variant in the coding region of the ATP1B4gene may play little or no role in the development of PD in Chinese Han population. Objective:Systematic analysis of all the coding region in the F-box protein42gene(FBXO42) was performed to determine whether mutations in this gene are associated with Parkinson’s disease (PD) in a Chinese Han population.Methods:All the coding region and intron/exon boundaries of the FBXO42gene of151PD patients were analyzed using polymerase chain reaction-single strand conformation polymorphism and sequencing. The genotype and allele frequency distributions between enlarged PD cohort (316cases and295matched controls) were evaluated by statistical analysis, and haplotype analysis was also performed to estimate the association of FBXO42haplotypes with PD.Results:A novel variant c.1407T>C was identified in a78-year-old male patient with sporadic PD, and it was absent in all controls. The variant does not change amino acid (p.S469S) or splicing. Three known single nucleotide variants, including c.15G> A (p.S5S, rs2273311), C.1411C> G (p.P471A, rs12069239), and C.1525G> A (p.A509T, rs35196193) were found in our PD cohort, and all the three variants do not change splicing. None of the three known variants showed statistically significant difference in either genotypic or allelic distributions between patient and control groups (all P>0.05). Haplotype analysis found that a common haplotype G-C-G for the three variants (rs2273311-rs12069239-rs35196193) increased the risk of PD (P=0.002, OR=1.69,95%CI=1.06-2.71), and the association remained to be statistically significant after Bonferroni correction (P=0.008).Conclusions:Though the variants in the coding region of the FBXO42gene may not be associated with PD, but a common haplotype in this gene may contribute to the susceptibility to PD at least in this Chinese Han population.