P268S in NOD2 associates with susceptibility to Parkinson’s disease in Chinese population

Abstract

BackgroundThe cause of almost all cases of Parkinson’s disease (PD) remains unknown. Recent years have seen an explosion in the rate of discovery of genetic defects linked to PD. Different racial and geographical populations may have different distributions of genetic variants.MethodsIn the current study, we screened the following genetic variants, including some rare mutations and single nucleotide polymorphisms (SNPs), in a pedigree and cases-controls. To best of our knowledge, we first screened these variants known to be associated with neurodegeneration disease, E46K (rs104893875) in SNCA, A1442P in LRRK2, IVS9 in PARK2, A350V in SLC41A1, P268S (rs2066842), R702W (rs2066844), G908R (rs2066845), 1007fs (rs2066847) in NOD2 and G2385R (rs34778348) in LRRK2 from southern China population. Genotyping was performed by jointly using primers overlapping polymerase chain reaction (PCR) site-directed mutagenesis, restriction fragment length polymorphism (RFLP), and capillary electrophoresis (CE).ResultsWe didn’t discover above 9 variants in the family members of the pedigree. Furthermore, of 237 patients with sporadic Parkinson’s disease and 190 controls, no heterozygosity or homozygosity were found from E46K, A1442P, A350V, R702W, G908R, or 1007fs but heterozygosity onto G2385R, IVS9, and P268S. No significant difference between cases and controls was found in both allele frequency (P = 0.572) and genotype frequency (P = 0.348) of IVS9. However, significant differences in genotype frequency (P = 0.009) of G2385R were consistent with prior observation. Eight patients with Parkinson’s disease (2 women and 6 men are over the age of 50 years at onset of PD) carried the P268S heterozygous variation in NOD2. There was no heterozygosity or homozygosity of P268S in the controls. Genotype frequency of P268S (P = 0.0450) had significant differences.ConclusionsOur results suggested that the P268S variant in NOD2 might be a risk factor for susceptibility to sporadic Parkinson’s disease in Chinese populations. It also implied that the inflammatory response may play a role in PD.

RETRACTED ARTICLE: Association between nucleotide-binding oligomerization domain protein 2 ( NOD2 ) gene polymorphisms and Parkinson’s disease (PD) susceptibility

“…Furthermore, NOD2 polymorphisms are proved to be associated with PD risk [27]. Ma et al find that NOD2 P268S polymorphism might play a role in sporadic PD susceptibility based on Chinese population and meanwhile prove that inflammatory response involve in PD [28]. In 2002, a French team published an analysis of NOD2 gene by direct DNA sequencing in 453 patients with CD and detected NOD2 SNP rs72796353, which was identified as potential disease-causing mutation [29].…”

Parkin targets NOD2 to regulate astrocyte endoplasmic reticulum stress and inflammation

“…Although, the role of NOD signaling in Parkin has not been extensively explored, an association with polymorphisms of NOD2 could potentially be associated with sporadic PD (Bialecka et al, 2007;Ma et al, 2013), although this finding has also been questioned (Appenzeller et al, 2012). Another potential link between NOD2 with increased susceptibility to PD could hypothetically be through the multifunctional protein kinase LRRK2.…”

Association study of TREM2 polymorphism rs75932628 with leucoaraiosis or Parkinson's disease in the Han Chinese population

“…Genomic DNA of all participants was isolated from peripheral whole blood using a MagCore Genomic DNA Whole Blood Kit and HF-16 extractor (RBC Bioscience, Taiwan), as previously published. 9 Genotyping of rs75932628-T (p.R47H) was conducted by molecular beacon real-time PCR using an ABI 7500 Fast Real-Time PCR System (Applied Biosystems, Foster City, California, USA) and then confirmed by Sanger sequencing using an ABI 3730XL automatic sequencer (Applied Biosystems, Foster City, California, USA). Sequences of primers and molecular beacons are given in table 2 .…”