title: Associations of PARP-1 variant rs1136410 with PARP activities, oxidative DNA damage, and the risk of age-related cataract in a Chinese Han population: A two-stage case-control analysis.
abstract: OBJECTIVE
  To investigate whether a single nucleotide polymorphism (SNP) rs1136410 in the poly (ADP-ribose) polymerase-1 (PARP-1) gene was associated with PARP activities, 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels, and the risk of age-related cataract (ARC) in a Chinese Han population.
  
  
  METHODS
  In this two-stage case-control study with a total of 1010 ARC patients and 1045 controls, SNP rs1136410 was genotyped by high-resolution melting analyses (HRM). PARP activities and 8-OHdG levels in peripheral blood mononuclear cells (PBMCs) were determined by ELISA kits.
  
  
  RESULTS
  In discovery, replication, and their merged sets, the variant genotypes (AG+GG) of SNP rs1136410 were significantly associated with an increased risk of ARC under a dominant model (Adjusted odds ratio (OR)=1.42, Padj=0.001 for the merged set). This association was further identified in subtype analyses for cortical ARC (Adjusted OR=1.69, Padj<0.001). In subgroup analyses, we identified a significant interaction between SNP rs1136410 and smoking habit in increasing ARC risk (Pinter=0.019). Moreover, ARC patients had lower activities of PARP and higher levels of 8-OHdG than controls. There were significant correlations of SNP rs1136410 with decreased PARP activities and increased 8-OHdG levels in controls and patients with cortical ARC.
  
  
  CONCLUSIONS
  This study suggests that SNP rs1136410 may confer susceptibility to ARC by affecting PARP activities and oxidative DNA damage.
authors.affiliation: Department of Clinical Laboratory, Children's Hospital of Zhengzhou, Zhengzhou, Henan, China. Electronic address: nhcui2016@163.com.
authors.forename: Ning-Hua
authors.initials: NH
authors.lastname: Cui
authors.affiliation: Department of Corneal, Hankou Aier Eye Hospital, Wuhan, Hubei, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Qiao
authors.affiliation: Department of Cataract, Hankou Aier Eye Hospital, Wuhan, Hubei, China.
authors.forename: Xiao-Ke
authors.initials: XK
authors.lastname: Chang
authors.affiliation: Department of Ophthalmology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wei
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000368:Aged; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002386:Cataract / Q000201:enzymology* / Q000235:genetics*; D002681:China; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D000071137:Poly (ADP-Ribose) Polymerase-1 / Q000235:genetics* / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D000080242:8-Hydroxy-2'-Deoxyguanosine; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D003849:Deoxyguanosine
keywords: Age-related cataract; Oxidative DNA damage; PARP activity; rs1136410