title: Interaction of CARD14, SENP1 and VEGFA polymorphisms on susceptibility to high altitude polycythemia in the Han Chinese population at the Qinghai-Tibetan Plateau.
abstract: High altitude polycythemia (HAPC) is a serious public health problem among Han Chinese immigrants to the Qinghai-Tibetan Plateau. This study aims to explore the genetic basis of HAPC in the Han Chinese population. 484 male subjects (234 patients and 250 controls) were enrolled in this study. Genotyping was performed for polymorphisms of I/D in ACE, C1772T and G1790A in exon 12 of HIF-1α, rs2567206 in CYP1B1, rs726354 in SENP1, rs3025033 in VEGFA, rs7251432 in HAMP, rs2075800 in HSPA1L and rs8065364 in CARD14. Gene-gene interaction was assessed by multifactor dimensionality reduction. A significant association was seen between CARD14 polymorphism rs8065364 and risk of HAPC development in male Han Chinese, and the C allele of rs8065364 was a risk factor (odds ratio (OR)=1.59, 95% confidence interval (95% CI)=1.21-2.08). Gene-gene interaction analysis indicated that a synergistic relationship existed between rs3025033 and rs8065364 (1.00%), rs3025033 and rs726354 (0.18%), and rs726354 and rs8065364 (0.17%). The combination of rs8065364 in CARD14, rs3025033 in VEGFA and rs726354 in SENP1 was the best model to predict HAPC development in this study (testing accuracy=0.6183, p=0.0010, cross-validated consistency=10/10). Genetic interactions of SNPs in CARD14, SENP1 and VEGFA might represent a functional mechanism in the pathogenesis of HAPC.
authors: Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Third Military Medical University, Chongqing 400038, China; Key Laboratory of High Altitude Medicine, Third Military Medical University, Ministry of Education, Chongqing 400038, China; Key Laboratory of High Altitude Medicine, PLA, Chongqing 400038, China.
authors: Yu
authors: Y
authors: Chen
authors: Department of Pathophysiology and High Altitude Pathology, College of High Altitude Military Medicine, Third Military Medical University, Chongqing 400038, China; Key Laboratory of High Altitude Medicine, Third Military Medical University, Ministry of Education, Chongqing 400038, China; Key Laboratory of High Altitude Medicine, PLA, Chongqing 400038, China.
authors: Chunhua
authors: C
authors: Jiang
authors: Department of Military Medical Geography, College of High Altitude Military Medicine, Third Military Medical University, Chongqing 400038, China; Key Laboratory of High Altitude Medicine, Third Military Medical University, Ministry of Education, Chongqing 400038, China; Key Laboratory of High Altitude Medicine, PLA, Chongqing 400038, China.
authors: Yongjun
authors: Y
authors: Luo
authors: Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Third Military Medical University, Chongqing 400038, China; Key Laboratory of High Altitude Medicine, Third Military Medical University, Ministry of Education, Chongqing 400038, China; Key Laboratory of High Altitude Medicine, PLA, Chongqing 400038, China.
authors: Fuyu
authors: F
authors: Liu
authors: Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Third Military Medical University, Chongqing 400038, China; Key Laboratory of High Altitude Medicine, Third Military Medical University, Ministry of Education, Chongqing 400038, China; Key Laboratory of High Altitude Medicine, PLA, Chongqing 400038, China. Electronic address: gaoy66@yahoo.com.
authors: Yuqi
authors: Y
authors: Gao
mesh_terms: D000328:Adult; D000483:Alleles; D000531:Altitude; D000532:Altitude Sickness / Q000150:complications / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D044466:Asian People; D053468:CARD Signaling Adaptor Proteins / Q000235:genetics*; D016022:Case-Control Studies; D003546:Cysteine Endopeptidases; D010450:Endopeptidases / Q000235:genetics*; D004843:Epistasis, Genetic; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D006162:Guanylate Cyclase / Q000235:genetics*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D064451:Hepcidins / Q000235:genetics; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics; D015810:Linkage Disequilibrium; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D016017:Odds Ratio; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011086:Polycythemia / Q000150:complications / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D018609:Tibet; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: D053468:CARD Signaling Adaptor Proteins; C578702:HAMP protein, human; C497442:HIF1A protein, human; D018840:HSP70 Heat-Shock Proteins; C543454:HSPA1L protein, human; D064451:Hepcidins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008565:Membrane Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D010450:Endopeptidases; C404512:SENP1 protein, human; C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A; D003546:Cysteine Endopeptidases; C426243:CARD14 protein, human; D006162:Guanylate Cyclase
keywords: High altitude exposure; High altitude polycythemia; High resolution melting; Multifactor dimensionality reduction; Polymorphism