title: P268S in NOD2 associates with susceptibility to Parkinson's disease in Chinese population.
abstract: BACKGROUND
  The 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.
  
  
  METHODS
  In 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).
  
  
  RESULTS
  We 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.
  
  
  CONCLUSIONS
  Our 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.
authors: Department of Neurology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian 361003, China.
authors: Qilin
authors: Q
authors: Ma
authors: Xingkai
authors: X
authors: An
authors: Zhiming
authors: Z
authors: Li
authors: Huanjing
authors: H
authors: Zhang
authors: Wenqing
authors: W
authors: Huang
authors: Liangliang
authors: L
authors: Cai
authors: Peng
authors: P
authors: Hu
authors: Qing
authors: Q
authors: Lin
authors: Chi-Meng
authors: CM
authors: Tzeng
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D002681:China; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D010300:Parkinson Disease / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein
references: Science. 2003 Oct 31;302(5646):819-22
references: 14593166
references: Lancet Neurol. 2009 Apr;8(4):382-97
references: 19296921
references: Annu Rev Biochem. 2005;74:29-52
references: 15952880
references: Arch Neurol. 2006 Jun;63(6):826-32
references: 16769863
references: Eur J Hum Genet. 2010 Dec;18(12):1356-9
references: 20683486
references: Ann Neurol. 2006 Oct;60(4):414-9
references: 16969854
references: Neuromolecular Med. 2002;2(3):299-309
references: 12622408
references: Arch Neurol. 2006 Mar;63(3):328-34
references: 16533959
references: Zhonghua Nei Ke Za Zhi. 2005 Mar;44(3):210-2
references: 15840263
references: Parkinsonism Relat Disord. 2004 May;10 Suppl 1:S3-7
references: 15109580
references: J Hum Genet. 2002;47(9):469-72
references: 12202985
references: Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7531-6
references: 9207126
references: J Biol Chem. 2006 Feb 10;281(6):3204-9
references: 16339143
references: Science. 1997 Jun 27;276(5321):2045-7
references: 9197268
references: Ann N Y Acad Sci. 2003 Jun;991:1-14
references: 12846969
references: J Biol Chem. 2008 Jun 6;283(23):16235-47
references: 18367447
references: Lancet Neurol. 2007 Jul;6(7):652-62
references: 17582365
references: Mov Disord. 2007 May 15;22(7):982-9
references: 17427941
references: Proc Natl Acad Sci U S A. 2003 Mar 18;100(6):3455-60
references: 12626759
references: Hum Mol Genet. 2004 Apr 1;13 Spec No 1:R127-33
references: 14976155
references: Nature. 2001 May 31;411(6837):603-6
references: 11385577
references: Nat Genet. 1998 Feb;18(2):106-8
references: 9462735
references: Am J Med Genet B Neuropsychiatr Genet. 2010 Jan 5;153B(1):229-34
references: 19475582
references: Neurosci Lett. 2005 Aug 26;384(3):327-9
references: 15955629
references: Arch Neurol. 2000 Apr;57(4):501-3
references: 10768624
references: Am J Med Genet B Neuropsychiatr Genet. 2005 Feb 5;133B(1):88-92
references: 15635591
references: Arthritis Rheum. 2002 Jun;46(6):1629-33
references: 12115195
references: J Neuropathol Exp Neurol. 1996 Mar;55(3):259-72
references: 8786384
references: Ann Neurol. 2004 Feb;55(2):164-73
references: 14755719
references: N Engl J Med. 2000 May 25;342(21):1560-7
references: 10824074
references: Neuroreport. 2007 Feb 12;18(3):273-5
references: 17314670
references: Lancet. 2005 Feb 12-18;365(9459):595-7
references: 15708103
references: J Neurol Neurosurg Psychiatry. 1992 Mar;55(3):181-4
references: 1564476
references: Eur J Hum Genet. 2003 Jan;11(1):6-16
references: 12529700
references: Int J Colorectal Dis. 2012 Nov;27(11):1465-72
references: 22426692
references: Exp Mol Med. 2006 Aug 31;38(4):333-47
references: 16953112
references: Neuron. 2003 Sep 11;39(6):889-909
references: 12971891
references: J Biol Chem. 2001 Feb 16;276(7):4812-8
references: 11087742
references: Gastroenterology. 2003 Jan;124(1):140-6
references: 12512038
references: Nat Rev Immunol. 2003 May;3(5):371-82
references: 12766759
references: Eur J Neurol. 2008 Mar;15(3):301-5
references: 18201193
references: J Biol Chem. 2003 Feb 21;278(8):5509-12
references: 12514169
references: Neurosci Res. 2007 Mar;57(3):473-6
references: 17174426
references: Neuron. 2002 Aug 1;35(3):419-32
references: 12165466
references: Neurology. 2002 Apr 23;58(8):1239-46
references: 11971093
references: Trends Neurosci. 2006 May;29(5):286-93
references: 16616379
references: Aliment Pharmacol Ther. 2003 Jun 15;17(12):1465-70
references: 12823148
references: Nat Genet. 2000 Jul;25(3):302-5
references: 10888878