ABSTRACT
Genome-wide association studies have reported numerous candidate loci associated with Parkinson's disease (PD). NUCKS1 and INPP5K are two such candidate loci, although they have rarely been reported in Asian populations. To explore these potential genes for PD susceptibility, we investigated the association between PD and two SNPs, rs823114 and rs1109303, located on the NUCKS1 and INPP5K genes, respectively, in the Han population of northern China. We genotyped the two SNPs using the multiplex PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) technique. A total of 685 subjects including 322 sporadic PD patients and 363 healthy controls were recruited from the population. After Bonferroni correction, our results suggested that there was a significant association of a minor allele (G) in rs823114 with reduced risk of PD development (P = 0.017, OR = 0.768, 95%CI = 0.618 - 0.955), and the difference in genotypes between the PD patients and healthy controls was significant under the dominant model (GA + GG vs. AA). After stratification by gender, males had a lower risk than females (P = 0.008, OR = 0.666, 95%CI = 0.495 - 0.898). However, the distribution of genotype frequency exhibited no significant differences between the PD and control groups (P > 0.025) in INPP5K rs1109303 (P = 0.048, OR = 0.806, 95%CI = 0.650 - 0.998). We conclude that NUCKS1 rs823114 indicates a decreased risk of susceptibility to PD and shows a male genetic distribution bias in the Han Chinese population.
Subject(s)
Nuclear Proteins/genetics , Parkinson Disease/genetics , Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases/genetics , Phosphoproteins/genetics , Aged , Alleles , Asian People/genetics , Case-Control Studies , China , Ethnicity/genetics , Female , Gene Frequency/genetics , Genetic Association Studies , Genetic Predisposition to Disease/genetics , Genome-Wide Association Study/methods , Humans , Male , Middle Aged , Nuclear Proteins/metabolism , Parkinson Disease/physiopathology , Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases/metabolism , Phosphoproteins/metabolism , Polymorphism, Single Nucleotide/genetics , Risk FactorsABSTRACT
The causal mutations and genetic polymorphisms associated with susceptibility to Parkinson's disease (PD) have been extensively described. To explore the potential contribution of insertion (I)/deletion (D) polymorphisms (indels) to the risk of PD in a Chinese population, we performed genetic analyses of indel loci in ACE, DJ-1, and GIGYF2 genes. Genomic DNA was extracted from venous blood of 348 PD patients and 325 age- and sex-matched controls without neurodegenerative disease. Genotyping of the indel loci was performed by fragment length analysis after PCR and DNA sequencing. Our results showed a statistically significant association for both allele X (alleles without 5) vs. 5 (odds ratio = 1.378, 95% confidence interval = 1.112-1.708, P = 0.003) and genotype 5/X+X/X vs. 5/5 (odds ratio = 1.681, 95% confidence interval = 1.174-2.407, P = 0.004) in the GIGYF2 locus; however, no significant differences were detected for the ACE and DJ-1 indels. After stratification by gender, no significant differences were observed in any indels. These results indicate that the GIGYF2 indel may be associated with increased risk of PD in northern China.
