title: Effect of High-Density Lipoprotein Metabolic Pathway Gene Variations and Risk Factors on Neovascular Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy in China.
abstract: OBJECTIVE
  To investigate the effect of genetic variants in the high-density lipoprotein (HDL) metabolic pathway and risk factors on neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) in China.
  
  
  METHODS
  A total of 742 Chinese subjects, including 221 controls, 230 cases with nAMD, and 291 cases with PCV, were included in the present study. Five single nucleotide polymorphisms (SNPs) from three genes in the HDL metabolic pathway (HDLMP) including cholesteryl ester transfer protein (CETP), hepatic lipase (LIPC) and lipoprotein lipase (LPL) were genotyped in all study subjects with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Risk factors including gender, hypertension, hyperlipidemia, diabetes mellitus, and coronary artery disease were identified. Chi-square tests or Fisher's exact tests were applied to discover associations between SNPs and risk factors for PCV and nAMD. Gene-gene interactions and gene-environment interactions were evaluated by the multifactor-dimensionality reduction (MDR) method.
  
  
  RESULTS
  CETP rs3764261 were significantly associated with an increased risk for PCV (odds ratio (OR) = 1.444, P = 0.0247). LIPC rs1532085 conferred an increased risk for PCV (OR = 1.393, P = 0.0094). We found no association between PCV and LPL rs12678919, LIPC rs10468017 or CETP rs173539. No association was found between five SNPs with nAMD. Regarding risk factors, females were found to have significantly decreased risks for both PCV and nAMD (P = 0.006 and 0.001, respectively). Coronary artery disease (CAD) was a risk factor in PCV patients but played a protective role in nAMD patients. Hyperlipidemia was associated with PCV but not with nAMD. Neither hypertension nor diabetes mellitus was associated with PCV or nAMD. The MDR analysis revealed that a three-locus model with rs12678919, rs1532085, and gender was the best model for nAMD, while a five-locus model consisting of rs10468017, rs3764261, rs1532085, gender, and hyperlipidemia was best for PCV.
  
  
  CONCLUSIONS
  Our large-sample study suggested that CETP rs3764261 conferred an increased risk for PCV. We also first found the association between rs1532085 and PCV. The result of present study also showed that gender and CAD are associated with PCV and nAMD. Significant association was found between hyperlipidemia and PCV but not nAMD.
authors.affiliation: Peking University People's Hospital, Ophthalmology Department, Beijing, China.|Key Laboratory of Vision Loss and Restoration, Ministry of Education, Beijing, China.|Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing, China.
authors.forename: Qingyu
authors.initials: Q
authors.lastname: Meng
authors.affiliation: Peking University People's Hospital, Ophthalmology Department, Beijing, China.|Key Laboratory of Vision Loss and Restoration, Ministry of Education, Beijing, China.|Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing, China.
authors.forename: Lvzhen
authors.initials: L
authors.lastname: Huang
authors.affiliation: Peking University People's Hospital, Ophthalmology Department, Beijing, China.|Key Laboratory of Vision Loss and Restoration, Ministry of Education, Beijing, China.|Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing, China.
authors.forename: Yaoyao
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Peking University People's Hospital, Ophthalmology Department, Beijing, China.|Key Laboratory of Vision Loss and Restoration, Ministry of Education, Beijing, China.|Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing, China.
authors.forename: Yujing
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Peking University People's Hospital, Ophthalmology Department, Beijing, China.|Key Laboratory of Vision Loss and Restoration, Ministry of Education, Beijing, China.|Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Peking University People's Hospital, Ophthalmology Department, Beijing, China.|Key Laboratory of Vision Loss and Restoration, Ministry of Education, Beijing, China.|Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing, China.
authors.forename: Wenzhen
authors.initials: W
authors.lastname: Yu
authors.affiliation: Peking University People's Hospital, Ophthalmology Department, Beijing, China.|Key Laboratory of Vision Loss and Restoration, Ministry of Education, Beijing, China.|Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing, China.
authors.forename: Mingwei
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Peking University People's Hospital, Ophthalmology Department, Beijing, China.|Key Laboratory of Vision Loss and Restoration, Ministry of Education, Beijing, China.|Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing, China.
authors.forename: Xiaoxin
authors.initials: X
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002681:China; D002829:Choroid / Q000473:pathology; D020256:Choroidal Neovascularization / Q000235:genetics* / Q000473:pathology; D004843:Epistasis, Genetic / Q000235:genetics; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008075:Lipoproteins, HDL / Q000235:genetics*; D008297:Male; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D057135:Wet Macular Degeneration / Q000235:genetics* / Q000473:pathology
chemical_list: D008075:Lipoproteins, HDL