title: Associations of 6p21.3 Region with Age-related Macular Degeneration and Polypoidal Choroidal Vasculopathy.
abstract: Neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) are leading causes of blindness in aging populations. This study was conducted to investigate the associations of chromosome 6p21.3 region, including CFB-SKIV2L-TNXB-FKBPL-NOTCH4 genes, with both neovascular AMD and PCV. Six single nucleotide polymorphisms (SNPs) in this region and two known AMD-associated SNPs in CFH (rs800292) and HTRA1 (rs11200638) were genotyped in a Han Chinese cohort composed of 490 neovascular AMD patients, 419 PCV patients and 1316 controls. Among the SNPs, TNXB rs12153855 and FKBPL rs9391734 conferred an increased susceptibility to neovascular AMD (P = 2.8 × 10(-4) and 0.001, OR = 1.80 and 1.76, respectively), while SKIV2L exerted a protective effect on neovascular AMD (P = 2.2 × 10(-4), OR = 0.49). Rs12153855C and rs9391734A alleles could further increase the susceptibility to AMD in subjects with rs800292, rs11200638 and rs429608 risk alleles. However, only the association of SKIV2L rs429608 remained significant after adjusting for rs800292, rs11200638 and the other 5 SNPs. The protective haplotype AATGAG exhibited significant association with neovascular AMD (permutation P = 0.015, OR = 0.34). None of the SNPs in this region was associated with PCV. Association profiles of 6p21.3 region showed discrepancy between neovascular AMD and PCV, indicating possible molecular and pathological differences between these two retinal disorders.
authors: Sichuan Provincial Key Laboratory for Human Disease Gene Study, School of Medicine, Sichuan Academy of Medical Sciences &Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.|College of Life Science and Engineering, Southwest Jiaotong University, Chengdu, China.
authors: Zimeng
authors: Z
authors: Ye
authors: Sichuan Provincial Key Laboratory for Human Disease Gene Study, School of Medicine, Sichuan Academy of Medical Sciences &Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.|Health Management Center, Sichuan Provincial People's Hospital, Chengdu, China.
authors: Ping
authors: P
authors: Shuai
authors: Sichuan Provincial Key Laboratory for Human Disease Gene Study, School of Medicine, Sichuan Academy of Medical Sciences &Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
authors: Yaru
authors: Y
authors: Zhai
authors: Sichuan Provincial Key Laboratory for Human Disease Gene Study, School of Medicine, Sichuan Academy of Medical Sciences &Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.|Department of ophthalmology, Sichuan Provincial People's Hospital, Chengdu, China.
authors: Fang
authors: F
authors: Li
authors: Sichuan Provincial Key Laboratory for Human Disease Gene Study, School of Medicine, Sichuan Academy of Medical Sciences &Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
authors: Lingxi
authors: L
authors: Jiang
authors: Sichuan Provincial Key Laboratory for Human Disease Gene Study, School of Medicine, Sichuan Academy of Medical Sciences &Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.|College of Life Science and Engineering, Southwest Jiaotong University, Chengdu, China.
authors: Fang
authors: F
authors: Lu
authors: Zhongshan Ophthalmic Center, Guangzhou, China.
authors: Feng
authors: F
authors: Wen
authors: Sichuan Provincial Key Laboratory for Human Disease Gene Study, School of Medicine, Sichuan Academy of Medical Sciences &Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
authors: Lulin
authors: L
authors: Huang
authors: Sichuan Provincial Key Laboratory for Human Disease Gene Study, School of Medicine, Sichuan Academy of Medical Sciences &Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.|Health Management Center, Sichuan Provincial People's Hospital, Chengdu, China.
authors: Dingding
authors: D
authors: Zhang
authors: Sichuan Provincial Key Laboratory for Human Disease Gene Study, School of Medicine, Sichuan Academy of Medical Sciences &Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
authors: Xiaoqi
authors: X
authors: Liu
authors: Sichuan Provincial Key Laboratory for Human Disease Gene Study, School of Medicine, Sichuan Academy of Medical Sciences &Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
authors: Ying
authors: Y
authors: Lin
authors: Sichuan Provincial Key Laboratory for Human Disease Gene Study, School of Medicine, Sichuan Academy of Medical Sciences &Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.|Clinical Medicine Department, Luzhou Medical College, Luzhou, China.
authors: Huaichao
authors: H
authors: Luo
authors: Sichuan Provincial Key Laboratory for Human Disease Gene Study, School of Medicine, Sichuan Academy of Medical Sciences &Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
authors: Houbin
authors: H
authors: Zhang
authors: Sichuan Provincial Key Laboratory for Human Disease Gene Study, School of Medicine, Sichuan Academy of Medical Sciences &Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.|College of Life Science and Engineering, Southwest Jiaotong University, Chengdu, China.
authors: Xianjun
authors: X
authors: Zhu
authors: Sichuan Provincial Key Laboratory for Human Disease Gene Study, School of Medicine, Sichuan Academy of Medical Sciences &Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.|Department of ophthalmology, Sichuan Provincial People's Hospital, Chengdu, China.
authors: Zhengzheng
authors: Z
authors: Wu
authors: Sichuan Provincial Key Laboratory for Human Disease Gene Study, School of Medicine, Sichuan Academy of Medical Sciences &Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.|College of Life Science and Engineering, Southwest Jiaotong University, Chengdu, China.|Sichuan Translational Medicine Hospital, Chinese Academy of Sciences, Chengdu, China.
authors: Zhenglin
authors: Z
authors: Yang
authors: Sichuan Provincial Key Laboratory for Human Disease Gene Study, School of Medicine, Sichuan Academy of Medical Sciences &Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.|Sichuan Translational Medicine Hospital, Chinese Academy of Sciences, Chengdu, China.
authors: Bo
authors: B
authors: Gong
authors: Sichuan Provincial Key Laboratory for Human Disease Gene Study, School of Medicine, Sichuan Academy of Medical Sciences &Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.|College of Life Science and Engineering, Southwest Jiaotong University, Chengdu, China.|Sichuan Translational Medicine Hospital, Chinese Academy of Sciences, Chengdu, China.
authors: Yi
authors: Y
authors: Shi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016022:Case-Control Studies; D020256:Choroidal Neovascularization / Q000235:genetics* / Q000473:pathology; D002896:Chromosomes, Human, Pair 6; D004265:DNA Helicases / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D056426:Genetic Loci; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D020104:Immunophilins / Q000235:genetics; D015810:Linkage Disequilibrium; D008268:Macular Degeneration / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011518:Proto-Oncogene Proteins / Q000235:genetics; D000074562:Receptor, Notch4; D051880:Receptors, Notch / Q000235:genetics; D022021:Tacrolimus Binding Proteins; D019063:Tenascin / Q000235:genetics
chemical_list: C400101:FKBPL protein, human; C106075:NOTCH4 protein, human; D011518:Proto-Oncogene Proteins; D000074562:Receptor, Notch4; D051880:Receptors, Notch; D019063:Tenascin; C081865:tenascin X; D004265:DNA Helicases; D022021:Tacrolimus Binding Proteins; D020104:Immunophilins; C114718:SKIV2L protein, human