德美两国科学家近日在X染色体上发现某个遗传突变，可能有助解释为什么一些感染HIV的女性出现艾滋病的进程较缓。这是首次在性染色体上发现与艾滋病相关的遗传突变。研究论文8月14日发表在《美国人类遗传学杂志》（The American Journal of Human Genetics）上。
该项研究由德国莱布尼茨灵长类动物研究所的遗传学家Roman Siddiqui领导。研究人员在93名感染HIV的欧洲血统女性中发现，其中16位的X染色体上存在一个单核苷多态（SNP）。进一步研究发现，大多数带有该SNP的感染HIV的女性病情发展速度要比缺失该多态的女性和男性（其中一些带有该SNP）慢上近4倍。在艾滋病发展期间，这些女性体内的CD4细胞损失率较之其他女性显著降低，病毒量也较低。不过令人奇怪的是，这些女性中没有任何一名其两份X染色体上都存在该SNP。
Siddiqui表示，在X染色体上发现该SNP十分令人惊讶。他说：“我们从未期待有此发现，我认为现在我们发现了一个清楚的遗传学问题，将来必须对其进行关注。”
他目前正在计划一个项目，将在感染HIV的亚洲女性身上筛查该SNP，并将搜寻其它潜伏在性染色体上且有可能影响HIV感染和艾滋病进程的遗传宿主因子。他说：“我很确信一定存在着更多的性别特异性遗传突变，需要我们将它们找出来。”（生物谷Bioon.com）
生物谷推荐原始出处：
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.
