Zhu Linhao, Liu Lijun, He Xue, Yan Mengdan, Du Jieli, Yang Hua, Zhang Yuan, Yuan Dongya, Jin Tianbo
Key Laboratory of Molecular Mechanism and Intervention Research for Plateau Diseases of Tibet Autonomous Region Key Laboratory of High Altitude Environment and Genes Related to Diseases of Tibet Autonomous Region Key Laboratory for Basic Life Science Research of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi School of Life Sciences, Northwest University, Xi'an Inner Mongolia Medical University, Hohhot, Inner Mongolia, China.
Medicine (Baltimore). 2017 Mar;96(13):e6504. doi: 10.1097/MD.0000000000006504.
High-altitude pulmonary edema (HAPE) is a hypoxia-induced, life-threatening, pulmonary edema, which is characterized by exaggerated pulmonary hypertension caused by stress failure. ACYP2 was found to associated with telomere length, the aim of this study was to identify whether ACYP2 polymorphisms increase or decrease HAPE risk in the Chinese Han individuals.In present study, we have genotyped 7 single-nucleotide polymorphisms (SNPs) in ACYP2 to determine the haplotypes in a case-control study with 265 HAPE patients and 303 healthy individuals. Genotypes were determined using the Sequenom MassARRAY method. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression with adjustment for gender and age. We found 3 SNPs yielded significant evidence for association with HAPE risk which had not been investigated before. Rs6713088 was found to have a 1.85- and 1.30-fold increased risk of HAPE in the recessive and additive model. The GT of rs843752 also conferred an increased risk of HAPE (GT/TT: OR = 1.51, 95% CI: 1.05-2.16, P = 0.026) and the genotype frequency distributions of rs843752 had significant difference between cases and controls. The CC genotype of rs17045754 had a protect effect on HAPE patients, and it was found to have a 0.29-fold reduced risk of HAPE in the recessive model.Although additional, larger population-based studies are needed to confirm these findings, our study shed light on the association between ACYP2 variant and HAPE risk in Han Chinese population for the first time.
高原肺水肿(HAPE)是一种由缺氧引起的、危及生命的肺水肿,其特征是应激衰竭导致肺动脉高压加剧。研究发现ACYP2与端粒长度相关,本研究的目的是确定ACYP2基因多态性是否会增加或降低中国汉族个体患HAPE的风险。在本研究中,我们对ACYP2基因中的7个单核苷酸多态性(SNP)进行了基因分型,以确定其单倍型,该研究为病例对照研究,纳入了265例HAPE患者和303名健康个体。采用Sequenom MassARRAY方法确定基因型。通过无条件逻辑回归计算优势比(OR)和95%置信区间(CI),并对性别和年龄进行校正。我们发现有3个SNP提供了与HAPE风险相关的显著证据,而此前尚未对其进行过研究。发现在隐性和加性模型中,rs6713088患HAPE的风险分别增加了1.85倍和1.30倍。rs843752的GT基因型也增加了患HAPE的风险(GT/TT:OR = 1.51,95% CI:1.05 - 2.16,P = 0.026),并且rs843752的基因型频率分布在病例组和对照组之间存在显著差异。rs17045754的CC基因型对HAPE患者具有保护作用,发现在隐性模型中其患HAPE的风险降低了0.29倍。尽管需要更多基于人群的大规模研究来证实这些发现,但我们的研究首次揭示了ACYP2变异与中国汉族人群HAPE风险之间的关联。