德美兩國科學(xué)家近日在X染色體上發(fā)現(xiàn)某個(gè)遺傳突變，可能有助解釋為什么一些感染HIV的女性出現(xiàn)艾滋病的進(jìn)程較緩,。這是首次在性染色體上發(fā)現(xiàn)與艾滋病相關(guān)的遺傳突變,。研究論文8月14日發(fā)表在《美國人類遺傳學(xué)雜志》（The American Journal of Human Genetics）上。
該項(xiàng)研究由德國萊布尼茨靈長類動(dòng)物研究所的遺傳學(xué)家Roman Siddiqui領(lǐng)導(dǎo),。研究人員在93名感染HIV的歐洲血統(tǒng)女性中發(fā)現(xiàn),，其中16位的X染色體上存在一個(gè)單核苷多態(tài)（SNP）。進(jìn)一步研究發(fā)現(xiàn),，大多數(shù)帶有該SNP的感染HIV的女性病情發(fā)展速度要比缺失該多態(tài)的女性和男性（其中一些帶有該SNP）慢上近4倍,。在艾滋病發(fā)展期間，這些女性體內(nèi)的CD4細(xì)胞損失率較之其他女性顯著降低,，病毒量也較低,。不過令人奇怪的是，這些女性中沒有任何一名其兩份X染色體上都存在該SNP,。
Siddiqui表示,，在X染色體上發(fā)現(xiàn)該SNP十分令人驚訝。他說：“我們從未期待有此發(fā)現(xiàn),，我認(rèn)為現(xiàn)在我們發(fā)現(xiàn)了一個(gè)清楚的遺傳學(xué)問題，將來必須對(duì)其進(jìn)行關(guān)注,。”
他目前正在計(jì)劃一個(gè)項(xiàng)目,，將在感染HIV的亞洲女性身上篩查該SNP，并將搜尋其它潛伏在性染色體上且有可能影響HIV感染和艾滋病進(jìn)程的遺傳宿主因子,。他說：“我很確信一定存在著更多的性別特異性遺傳突變,，需要我們將它們找出來。”（生物谷Bioon.com）
生物谷推薦原始出處：
The American Journal of Human Genetics, Volume 85, Issue 2, 228-239, 14 August 2009 doi:10.1016/j.ajhg.2009.07.013
X Chromosomal Variation Is Associated with Slow Progression to AIDS in HIV-1-Infected Women
Roman A. Siddiqui1,8,,,Ulrike Sauermann2,8,Janine Altmüller3,Elfriede Fritzer4,Michael Nothnagel4,Nina Dalibor3,Jacques Fellay5,Franz-Josef Kaup2,Christiane Stahl-Hennig2,Peter Nürnberg3,6,7,Michael Krawczak4andMatthias Platzer1
1 Genome Analysis, Leibniz Institute for Age ResearchFritz Lipmann Institute, Beutenbergstr. 11, 07745 Jena, Germany
2 German Primate Center, Leibniz Institute for Primate Research, Kellnerweg 4, 37077 G?ttingen, Germany
3 Cologne Center for Genomics, University of Cologne, Zülpicher Strae 47, 50674 Cologne, Germany
4 Institute of Medical Informatics and Statistics, Christian-Albrechts-University, Brunswiker Str. 10, 24105 Kiel, Germany
5 Center for Human Genome Variation, Duke Institute for Genome Sciences & Policy, Duke University, Durham, NC 27710, USA
6 Center for Molecular Medicine Cologne, University of Cologne, Robert-Koch-Str. 21, 50931 Cologne, Germany
7 Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Zülpicher Strae 47, 50674 Cologne, Germany
AIDS has changed from a mostly male-specific health problem to one that predominantly affects females. Although sex differences in HIV-1 susceptibility are beyond doubt, the extent to which sex affects the onset and progression of AIDS has remained elusive. Here, we provide evidence for an influence of X chromosomal variation on the course of retroviral infection, both in HIV-1-infected patients and in the rhesus macaque model of AIDS. A two-stage, microsatellite-based GWAS of SIV-infected monkeys revealed MHC class I markers and a hitherto-unknown X chromosomal locus as being associated with a nominal score measuring progression to AIDS (Fisher's exact p < 106). The X chromosomal association was subsequently confirmed in HIV-1-infected patients with published SNP genotype data. SNP rs5968255, located at human Xq21.1 in a conserved sequence element near the RPS6KA6 and CYLC1 genes, was identified as a significant genetic determinant of disease progression in females (ANOVA p = 8.8 105), but not in males (p = 0.19). Heterozygous female carriers of the C allele showed significantly slower CD4 cell decline and a lower viral load at set point than TT homozygous females and than males. Inspection of HapMap revealed that the CT genotype is significantly more frequent among Asians than among Europeans or Africans. Our results suggest that, in addition to the individual innate and adaptive immunity status, sex-linked genetic variation impacts upon the rate of progression to AIDS. Elucidating the mechanisms underlying this sex-specific effect will promote the development of antiretroviral therapies with high efficacy in both sexes.
