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  • Title: Association analyses of variants of SIPA1L2, MIR4697, GCH1, VPS13C, and DDRGK1 with Parkinson's disease in East Asians.
    Author: Zou M, Li R, Wang JY, Wang K, Wang YN, Li Y, Ji FX, Sun SN, Huang SS, Fan HH, Huang CP, Zhang X, Zhu JH.
    Journal: Neurobiol Aging; 2018 Aug; 68():159.e7-159.e14. PubMed ID: 29622492.
    Abstract:
    A recent large-scale European-originated genome-wide association data meta-analysis followed by a replication study identified 6 new risk loci for Parkinson's disease (PD), which include rs10797576/SIPA1L2, rs117896735/INPP5F, rs329648/MIR4697, rs11158026/GCH1, rs2414739/VPS13C, and rs8118008/DDRGK1. However, whether these new loci are associated with PD in Asian populations remain elusive. The INPP5F is nonpolymorphic in Asians. The present study aimed to understand the effects of the other 5 new loci in a Han Chinese population comprising 579 sporadic PD patients and 642 controls. Significant associations with PD were observed in the variants of SIPA1L2 (p = 0.001) and VPS13C (p = 0.007), where the T (odd ratio [OR] = 1.484, 95% confidence interval [CI] 1.186-1.858) and A (OR = 1.362, 95% CI 1.087-1.707) alleles serve as the risk alleles, respectively. The genotype distributions in the SIPA1L2 and VPS13C variants were also different between the patients and controls (p = 0.002 and p = 0.023, respectively). In contrast, no significant association with PD was found in the variants of MIR4697, GCH1, and DDRGK1 either in allele or genotype frequencies. Noteworthy, a followed meta-analysis of East Asian studies suggested an association of the GCH1 variant with PD (p = 0.04, OR 1.08, 95% CI 1.00-1.16), while the other results are in line with those of our cohort. In conclusion, our study together with meta-analyses demonstrates that the variants of SIPA1L2 and VPS13C, potentially GCH1, but not of MIR4697 and DDRGK1, are associated with PD susceptibility in East Asians.
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