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Blood Cells Mol Dis. 2016 Mar;57:13-22. doi: 10.1016/j.bcmd.2015.11.005. Epub 2015 Nov 12.

Interaction of CARD14, SENP1 and VEGFA polymorphisms on susceptibility to high altitude polycythemia in the Han Chinese population at the Qinghai-Tibetan Plateau.

Author information

1
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.
2
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.
3
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.
4
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.

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.

KEYWORDS:

High altitude exposure; High altitude polycythemia; High resolution melting; Multifactor dimensionality reduction; Polymorphism

PMID:
26852650
DOI:
10.1016/j.bcmd.2015.11.005
[Indexed for MEDLINE]

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