Host genetics and HIV-1 viral load set-point in African-Americans
Host genetics and HIV-1 viral load set-point in African-Americans
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DOI：
10.1097/qad.0b013e328325d414
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发表时间：
2009-03-27
期刊：
影响因子：
3.8
通讯作者：
Tang, Jianming
中科院分区：
文献类型：
--
作者：
Shrestha, Sadeep;Aissani, Brahim;Tang, Jianming
目的：在最近的一项Euro-CHAVI队列中HIV-1感染个体的全基因组关联研究中，病毒载量设定点与6号染色体上人类主要组织相容性复合体（MHC）区域内的两个单核苷酸多态性（SNP）（rs 9264942和rs 2395029）定义的基因型密切相关。我们试图证实这一发现在非洲裔美国人和解决这些单核苷酸多态性是否在连锁不平衡与人类白细胞抗原（HILA）I类等位基因介导的先天性和适应性immunity.Design：我们的分析依赖于121名非洲裔美国青少年慢性HIV-1感染和季度免疫学和病毒学结果的措施，在没有治疗。使用基于PCR的技术对两个SNP沿着HLA I类等位基因进行基因分型。在单变量和多变量模型中检验了它们与HIV-1病毒载量设定点和纵向CD 4（+）和CD 8（+）CD 38（+）T细胞计数的相关性。在B*57中观察到有利的病毒学结果的一致关联（主要是B*5703），但在HCP 5位点不含rs 2395029 G等位基因，该等位基因与B*5701处于绝对连锁不平衡（在欧洲血统的个体中），而不是B* 5703。虽然rs 9264942和B*57（但不是rs 2395029 G）与非洲裔美国人中病毒载量设定点的控制明显相关，在非洲和欧洲血统的人群中精细定位MHC SNPs有助于揭示致病变异和潜在的功能机制。(C)2009年威科健康垂直酒吧Lippincott威廉姆斯&威尔金斯
Objective: In a recent genome-wide association study of HIV-1-infected individuals in the Euro-CHAVI cohort, viral load set-point was strongly associated with genotypes defined by two single nucleotide polymorphisms (SNPs) (rs9264942 and rs2395029) within the human major histocompatibility complex (MHC) region on chromosome 6. We attempted to confirm this finding in African-Americans and to address whether these SNPs are in linkage disequilibrium with human leukocyte antigen (HILA) class I alleles that mediate innate and adaptive immunity.Design: Our analyses relied on 121 African-American adolescents with chronic HIV-1 infection and quarterly immunological and virological outcome measures in the absence of therapy.Methods: PCR-based techniques were used to genotype two SNPs along with HLA class I alleles. Their associations with HIV-1 viral load set-point and longitudinal CD4(+) and CD8(+)CD38(+) T cell counts were tested in univariate and multivariable models.Results: The CC genotype at rs9264942 was associated with reduced viral load, but not with immunological outcomes or category of disease control. Consistent associations of favorable virologic outcomes were observed with B*57 (mostly B*5703) but not with rs2395029G allele at the HCP5 locus, which is in absolute linkage disequilibrium with B*5701 (in individuals of European descent), and not B*5703.Conclusion: Although rs9264942 and B*57 (but not rs2395029G) are clearly associated with control of viral load set-point among African-Americans, fine-mapping of MHC SNPs in populations of African and European descent should help reveal the causative variants and the underlying functional mechanisms. (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins