Rajput Charu, Arif Ehtesham, Vibhuti Arpana, Stobdan Tsering, Khan Amjad P, Norboo Tsering, Afrin Farhat, Qadar Pasha M A
Institute of Genomics and Integrative Biology, Delhi 110 007, India.
Biochem Biophys Res Commun. 2006 Sep 22;348(2):735-40. doi: 10.1016/j.bbrc.2006.07.116. Epub 2006 Jul 28.
Sojourners visiting high-altitude (HA) (>2500 m) are susceptible to HA disorders; on the contrary, HA natives are well adapted to the extreme hypoxic environment. High aldosterone levels are believed to be involved in HA disorders, we, therefore, envisaged role of CYP11B2 gene variants in HA adaptation and therefore investigated the -344T/C, intron-2 conversion (Iw/Ic), K173R, and A5160C polymorphisms. In addition, polymorphisms in AGT, AT1R, ATP1A1, ADRB2, and GSTP1 genes were also investigated. The study comprised of 662 subjects, comprising of 426 Himalayan highlanders (HLs) and 236 lowlanders (LLs). The -344T/C and K173R polymorphisms were found to be in complete linkage disequilibrium. The wild-type allele -344T and combination of wild-type homozygous genotypes between -344T/C, Iw/Ic, and A5160C polymorphisms, containing all the six wild-type alleles were over-represented in the HLs (p < 0.0001, and p = 0.008, respectively). The wild-type haplotypes -344T-Iw, -344T-5160A, and -344T-Iw-5160A also showed over-representation in the HLs (p < 0.0001). Furthermore, greater the number of wild-type alleles, lower was the ARR (p < 0.05). The genotype distribution in remaining genes did not differ. To conclude, the over-representation of wild-type -344T allele, genotype combinations and haplotypes of CYP11B2, and their correlation with lower aldosterone levels associate with HA adaptation in the HLs. Such an allelic presentation in sojourners may help them cope with adverse HA environment.
前往高海拔地区（HA，>2500米）的旅居者易患HA相关疾病；相反，高海拔地区的原住民对极端低氧环境具有良好的适应性。高醛固酮水平被认为与HA相关疾病有关，因此，我们设想CYP11B2基因变异在HA适应中的作用，进而研究了-344T/C、内含子2转换（Iw/Ic）、K173R和A5160C多态性。此外，还研究了AGT、AT1R、ATP1A1、ADRB2和GSTP1基因的多态性。该研究纳入了662名受试者，包括426名喜马拉雅高地人（HLs）和236名低地人（LLs）。发现-344T/C和K173R多态性处于完全连锁不平衡状态。野生型等位基因-344T以及-344T/C、Iw/Ic和A5160C多态性之间的野生型纯合基因型组合（包含所有六个野生型等位基因）在HLs中过度表达（分别为p < 0.0001和p = 0.008）。野生型单倍型-344T-Iw、-344T-5160A和-344T-Iw-5160A在HLs中也表现出过度表达（p < 0.0001）。此外，野生型等位基因数量越多，醛固酮比值（ARR）越低（p < 0.05）。其余基因的基因型分布没有差异。总之，野生型-344T等位基因、CYP11B2的基因型组合和单倍型的过度表达及其与较低醛固酮水平的相关性与HLs的HA适应有关。旅居者中的这种等位基因表现可能有助于他们应对不利的HA环境。
