<b><i>CCDC62</i></b> Variant rs12817488 Is Associated with the Risk of Parkinson's Disease in a Han Chinese Population

Abstract

It has been recently proposed by a genome-wide association study (GWAS) meta-analysis that the CCDC62 variant rs12817488 is a new risk locus associated with Parkinson's disease (PD). In this study, we aimed to investigate the association between rs12817488 and PD in a Chinese cohort. A total of 341 PD patients and 423 matched controls were recruited in Eastern China. Our results showed that the A allele of rs12817488 was significantly associated with an aggravated risk of PD (p = 0.006) and represented a major allele in contrast to a minor one in Caucasians. Genotype distributions also differed between PD patients and controls (p = 0.011 for AA/AG/GG). Further analysis showed that the association of rs12817488 with PD only existed in females. We also investigated the protein level of CCDC62 in peripheral blood mononuclear cells from 41 AA or GG carriers and found an apparently higher expression in PD patients carrying the AA genotype. A potential interaction was found between two estrogen-related loci, i.e. rs12817488/CCDC62 and rs2697962/PRDM2, particularly in the female stratum. In conclusion, our study demonstrated for the first time a significant association between the rs12817488 polymorphism and PD predisposition in a Chinese population with gender variations and provides new insight regarding the variant's protein expression and estrogen-related genetic interaction.

The single nucleotide polymorphism Rs12817488 is associated with Parkinson’s disease in the Chinese population

“…found there was no association between rs12817488 and PD in a larger cohort [14], but the other group reported that the A allele of rs12817488 was significantly associated with an aggravated risk of PD in Eastern China [15]. In contrast to Liu et al's studies [15], we found that the genotype and allele frequencies of rs12817488 were only associated with the LOPD group and the male patients. Therefore, replication of these studies in Chinese populations is necessary to validate the role of this locus in PD risk.…”

“…We found that this variant increases the risk of PD by approximately 1.6-fold, which is similar with the reports of other groups [15,17,21]. There are two previous, related studies in the Han Chinese population.…”

“…Liu et al investigated the protein level of CCDC62 in peripheral blood mononuclear cells from 41 AA or GG carriers and found an apparently higher expression in PD patients carrying the AA genotype. This suggests that CCDC62 might have a major function in this locus [15]. Further studies should be carried out to confirm this phenomenon.…”

Genetic analysis of indel markers in three loci associated with Parkinson's disease

“…Yu et al . found that a significant association only existed in males [ 56 ], while Liu et al . only found this association in a female population [ 57 ].…”

Possible association of CCDC62 rs12817488 polymorphism and Parkinson’s disease risk in Chinese population: a meta-analysis

“…Rs12817488 is localized in the intron of Coiled-coil domain containing 62 (CCDC62), and has been found to be associated with PD risk, but the overall and stratified subgroup results were controversial. Yu RL showed significant association only existed in male, while Liu RR found this only in female population 6 7 . However, Li NN found no relationship between rs12817488 and PD susceptibility 8 .…”