CYP17A1 and CYP2E1 variants associated with high altitude polycythemia in Tibetans at the Qinghai-Tibetan Plateau.
Tibetans adapt to high altitude environments through low blood hemoglobin concentrations. Previous work has identified that CYP17A1 and CYP2E1 genes exhibit evidence of local positive selection for this Tibetan high-altitude adaptation. Nevertheless, despite this apparent genetic advantage, some Tibetans still develop high altitude polycythemia (HAPC) yet the reasons for this remain unknown. We sought to determine if polymorphisms in CYP17A1 and CYP2E1 genes were associated with susceptibility to HAPC in Tibetans at the Qinghai-Tibetan Plateau in China. We enrolled 63 Tibetan HAPC patients and 131 healthy, age- and gender-matched control Tibetans. All subjects are from the Yushu area of Qinghai where the altitude is over 3500 m. Three SNPs of the CYP17A1 including rs3781287, rs11191548 and rs1004467, and four SNPs of CYP2E1 gene, including rs1536836, rs3813865, rs3813867 and rs743535, were genotyped by the Sequenom MassARRAY SNP assays. We discovered that SNP rs1004467 of the CYP17A1 gene and SNP rs3813865 of the CYP2E1 gene were significantly associated with HAPC risk. Furthermore, we identified a positive correlation between these two SNPs and plasma hemoglobin levels. Thus, taken together, our study is the first to our knowledge to show that polymorphisms in the rs1004467 SNP of CYP17A1 and rs3813865 SNP of CYP2E1 correlate with susceptibility to HAPC.
Research Center for High Altitude Medical Sciences, Qinghai University School of Medicine, Qinghai 810001, China; Department of Clinical Medicine, Qinghai University School of Medicine, Qinghai 810001, China.
Jin
J
Xu
Research Center for High Altitude Medical Sciences, Qinghai University School of Medicine, Qinghai 810001, China.
Ying-zhong
YZ
Yang
Research Center for High Altitude Medical Sciences, Qinghai University School of Medicine, Qinghai 810001, China.
Feng
F
Tang
Research Center for High Altitude Medical Sciences, Qinghai University School of Medicine, Qinghai 810001, China.
Qin
Q
Ga
Research Center for High Altitude Medical Sciences, Qinghai University School of Medicine, Qinghai 810001, China.
Tana
T
Wuren
Department of Hepatic-Biliary-Pancreatic Surgery, Qinghai University Affiliated Hospital, Qinghai 810001, China.
Zhan
Z
Wang
Research Center for High Altitude Medical Sciences, Qinghai University School of Medicine, Qinghai 810001, China.
Lan
L
Ma
Department of Internal Medicine, George E. Wahlen VA Medical Center; Salt Lake City, Utah, 84108 USA; Division of General Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah, 84132 USA; Molecular Medicine Program in the Eccles Institute of Human Genetics, Salt Lake City, Utah, USA, 84112 USA.
Matthew T
MT
Rondina
Research Center for High Altitude Medical Sciences, Qinghai University School of Medicine, Qinghai 810001, China. Electronic address: geriligao@hotmail.com.
Ri-li
RL
Ge
D000328:Adult; D000368:Aged; D000531:Altitude; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011086:Polycythemia / Q000235:genetics*; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics*; D018609:Tibet
D019392:Cytochrome P-450 CYP2E1; C501892:CYP17A1 protein, human; D013254:Steroid 17-alpha-Hydroxylase
CYP17A1; CYP2E1; High altitude polycythemia; Tibetans; Variants