三个不同海拔藏族群体HIF1A基因九个单核苷酸多态性位点研究  

Study of nine single nucleotide polymorphism loci of human HIF1A gene in three Tibetan groups

作　　者：柯金坤[1] 姚宇峰[1] 史磊[1] 于亮[1] 林克勤[1] 陶玉芬[1] 史荔[1] 易文[1] 黄小琴[1] 孙浩[1] 褚嘉祏[1] 

机构地区：[1]中国医学科学院&北京协和医学院医学生物学研究所遗传室,昆明650118

出　　处：《中华医学遗传学杂志》2010年第5期584-589,共6页Chinese Journal of Medical Genetics

基　　金：国家自然科学基金面上项目（30971578）;美国中华医学基金会资助项目（04-805）感谢为本研究提供样本的志愿者

摘　　要：目的研究不同海拔高度的低氧环境差异对基因缺氧诱导因子1a基因（hypoxia inducible factor 1 alpha，HIF1A）的选择作用。方法选取世居于西藏、青海、云南的3个不同海拔高度的藏族群体，利用聚合酶链反应一限制性片段长度多态性技术检测HIF1A基因的9个单核苷酸多态性（single nucleotide polymorphisms，SNP）位点。结果所有非同义突变SNP位点的基因型频率与等位基因型频率在3个藏族群体之间差异无统计学意义，而rs11549465位点的基因型频率在云南藏族分别与西藏藏族和青海藏族之间差异有统计学意义（P〈0．05）。4个内含子SNP位点基因型频率与等位基因频率在西藏藏族与青海藏族之间差异均无统计学意义；但在西藏藏族和青海藏族分别与云南藏族比较时，基因型频率与等位基因频率差异均有统计学意义（P〈0．05），且跟海拔差异有相关性。结论海拔高度不同引起的低氧环境差异有可能对HIF1A基因有选择作用。Objective To investigate the effect of hypoxia environment induced by altitude on hypoxia inducible factor 1α （HIF1A）gene. Methods Nine single nucleotide polymorphism （SNP） loci of the HIF1A gene from three Tibetan groups （Tibet, Qinghai Province and Yunnan Province） were genotyped using PCR restriction fragment length polymorpbism（PCR-RFLP） method. Results For non-synonymous mutation SNP site, there was no significant difference among the three Tibetan groups, except for SNP rs11549465 between Tibet Tibetan and Yunnan Tibetan, as well as between Qinghai Tibetan and Yunnan Tibetan. Frequencies of genotypes and alleles in rs4899056, rs1957757, rs10873142 and rs3783752 had significant differences between Tibet Tibetan and Yunnan Tibetan, and between Qinghai Tibetan and Yunnan Tibetan （all P〈0.05）. We also observed that the difference was negatively correlated with the altitude. Conclusion The results suggested that the HIF1A gene might be under hypoxie selection induced by high altitude in the three groups.

关 键 词：藏族群体 缺氧诱导因子1Α 单核苷酸多态性 低氧环境 海拔 限制性片段长 度多态性 

分 类 号：R686[医药卫生—骨科学]