Association analyses of variants of SIPA1L2, MIR4697, GCH1, VPS13C, and DDRGK1 with Parkinson's disease in East Asians

Neurobiol Aging. 2018 Aug:68:159.e7-159.e14. doi: 10.1016/j.neurobiolaging.2018.03.005. Epub 2018 Mar 10.

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.

Keywords: Association; DDRGK1; GCH1; MIR4697; Parkinson's disease; Polymorphism; SIPA1L2; VPS13C.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Aged
  • Asia, Eastern
  • Asian People / genetics
  • Carrier Proteins / genetics*
  • Female
  • GTP Cyclohydrolase / genetics*
  • GTPase-Activating Proteins / genetics*
  • Genetic Predisposition to Disease / genetics*
  • Genetic Variation / genetics*
  • Genome-Wide Association Study*
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Nuclear Proteins / genetics*
  • Parkinson Disease / etiology*
  • Parkinson Disease / genetics*
  • Proteins / genetics*

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • DDRGK1 protein, human
  • GTPase-Activating Proteins
  • MIRN4697 microRNA, human
  • MicroRNAs
  • Nuclear Proteins
  • Proteins
  • SIPA1 protein, human
  • VPS13C protein, human
  • GTP Cyclohydrolase