MKL1基因多态性与高原环境适应性的遗传关联研究

doi:10.16288/j.yczz.19-049

遗传 ›› 2019, Vol. 41 ›› Issue (7): 634-643.doi: 10.16288/j.yczz.19-049

MKL1基因多态性与高原环境适应性的遗传关联研究

张晴¹,平杰²,张昊翔³,康波³,李元丰²(),周钢桥^1,^2,⁴()

^1. 南京医科大学公共卫生学院流行病学系,南京 211166
^2. 中国人民解放军军事科学院军事医学研究院辐射医学研究所,蛋白质组学国家重点实验室,国家蛋白质科学中心(北京),北京 102206
^3. 中国人民解放军陆军第954医院,山南856100
^4. 南京医科大学全球健康中心,南京 211166

收稿日期:2019-02-25 修回日期:2019-05-06 出版日期:2019-07-20 发布日期:2019-05-23
通讯作者: 李元丰,周钢桥 E-mail:liyf_snp@163.com;zhougq114@126.com
作者简介:张晴,硕士研究生,专业方向：流行病与卫生统计学。E-mail: zhangqingah@163.com|平杰,博士研究生,专业方向：遗传学。E-mail: pingjie46@126.com
基金资助:
国家自然科学基金重点项目(81730055);中国科协青年人才托举工程项目资助(QNRC001)

Genetic association of MKL1 gene polymorphisms with the high-altitude adaptation

Zhang Qing¹,Ping Jie²,Zhang Haoxiang³,Kang Bo³, ²(),Zhou Gangqiao^1,^2,⁴()

^1. Department of Epidemiology, School of PublicHealth, Nanjing Medical University, Nanjing 211166, China
^2. State Key Laboratory of Proteomics, National Center for Protein Sciences at Beijing, Beijing Institute of Radiation Medicine, Beijing 1002206, China
^3. The No.954 Hospital of PLA, Shannan 856100, China
^4. Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China

Received:2019-02-25 Revised:2019-05-06 Online:2019-07-20 Published:2019-05-23
Contact: ,Zhou Gangqiao E-mail:liyf_snp@163.com;zhougq114@126.com
Supported by:
Supported by the National Natural Science Foundation of China(81730055);The Young Talent Cultivation Project of China(QNRC001)

摘要/Abstract

摘要：

高原环境适应性与遗传因素密切相关,已有多个基因被报道与高原环境适应性显著相关。巨核细胞白血病因子1(megakaryoblastic leukemia 1,MKL1)是一种转录调节因子,在平滑肌细胞的表型调变中发挥重要作用。为探讨MKL1基因是否与高原环境适应性相关,本研究进行了MKL1基因多态性与高原环境适应性的遗传关联分析。本研究招募了世居青藏高原的藏族人群(n = 595)和世居平原地区的汉族人群(n = 442),并采用MassARRAY阵列图谱技术对MKL1基因的多态性位点rs59098711进行基因分型,比较了其基因型及等位基因型在两组人群中的分布是否存在显著差异。结果发现,在藏、汉两组人群间rs59098711位点的基因型和等位基因型频率存在显著差异(P<0.05)。进一步通过与公共数据库比较发现,藏族人群中rs59098711的基因型及等位基因型的频率分布与其他人种存在显著差异(P<0.05)。生物信息学分析表明,rs59098711位点位于MKL1基因增强子区域,与MKL1基因表达的调控密切相关。同时,基于公共数据集进行的基因差异表达分析发现,MKL1基因在低压性缺氧环境中显著上调。以上研究结果表明,MKL1基因的多态性位点rs59098711与人类的高原适应能力存在相关性。

关键词: 高原环境适应性, MKL1, 单核苷酸多态性

Abstract:

Genetic factors are closely related to the high-altitude adaptation. Several candidate genes have been reported to be significantly associated with high-altitude adaptation. Megakaryocytic leukemia 1 (MKL1) is a transcriptional regulator, which plays crucial roles in the phenotypic modulation of smooth muscle cells. To explore whether MKL1 gene is involved in high-altitude adaptation, we performed genetic association study between MKL1 gene polymorphisms and high-altitude adaptation. We recruited 595 Tibetans from the Qinghai-Tibet plateau and 442 Hans living at low altitude. The SNP rs59098711 locus in the MKL1 gene was genotyped using the MassARRAY assays. We compared the genotypes and allele frequency distributions of rs59098711 between the Hans and Tibetans. The results showed that the genotypes of rs59098711 are significantly different between these two populations (P<0.05). We further compared the genotypes of rs59098711 between Tibetans and other ethnic groups using data from various public databases. We also observed that the genotypes of rs59098711 are significantly different between Tibetans and these other populations (P<0.05). Bioinformatics analyses suggested that rs59098711 could be located at the enhancer region and regulate the expression of the MKL1 gene. Additional study of gene expression data from available public datasets showed that MKL1 gene was up-regulated in a hypobaric hypoxic environment. Our results suggested that the genetic polymorphism rs59098711 locus of the MKL1 gene is associated with high-altitude adaption.

Key words: high-altitude adaptation, MKL1, single nucleotide polymorphism

张晴,平杰,张昊翔,康波,李元丰,周钢桥. MKL1基因多态性与高原环境适应性的遗传关联研究[J]. 遗传, 2019, 41(7): 634-643.

Zhang Qing,Ping Jie,Zhang Haoxiang,Kang Bo, ,Zhou Gangqiao. Genetic association of MKL1 gene polymorphisms with the high-altitude adaptation[J]. Hereditas(Beijing), 2019, 41(7): 634-643.

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MKL1基因多态性与高原环境适应性的遗传关联研究

Genetic association of MKL1 gene polymorphisms with the high-altitude adaptation

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