Brummel Sean S, Singh Kumud K, Maihofer Adam X, Farhad Mona, Qin Min, Fenton Terry, Nievergelt Caroline M, Spector Stephen A
*Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, MA; †University of California, San Diego, La Jolla, CA; ‡Rady Children's Hospital, San Diego, CA; and §Department of Psychiatry, University of California, San Diego, La Jolla, CA.
J Acquir Immune Defic Syndr. 2016 Apr 15;71(5):544-50. doi: 10.1097/QAI.0000000000000883.
Ancestry informative markers (AIMs) measure genetic admixtures within an individual beyond self-reported racial/ethnic (SRR) groups. Here, we used genetically determined ancestry (GDA) across SRR groups and examine associations between GDA and HIV-1 RNA and CD4 counts in HIV-positive children in the United States.
Forty-one AIMs, developed to distinguish 7 continental regions, were detected by real-time PCR in 994 HIV-positive, antiretroviral naive children. GDA was estimated comparing each individual's genotypes to allele frequencies found in a large set of reference individuals originating from global populations using STRUCTURE. The means of GDA were calculated for each category of SRR. Linear regression was used to model GDA on CD4 count and log10 RNA, adjusting for SRR and age.
Subjects were 61% black, 25% Hispanic, 13% white, and 1.3% Unknown. The mean age was 2.3 years (45% male), mean CD4 count of 981 cells per cubic millimeter, and mean log10 RNA of 5.11. Marked heterogeneity was found for all SRR groups with high admixture for Hispanics. In adjusted linear regression models, subjects with 100% European ancestry were estimated to have 0.33 higher log10 RNA levels (95% CI: 0.03 to 0.62, P = 0.028) and 253 CD4 cells per cubic millimeter lower (95% CI: -517 to 11, P = 0.06) in CD4 count, compared to subjects with 100% African ancestry.
Marked continental admixture was found among this cohort of HIV-infected children from the United States. GDA contributed to differences in RNA and CD4 counts beyond SRR and should be considered when outcomes associated with HIV infection are likely to have a genetic component.
祖先信息标记（AIMs）可测量个体内超出自我报告种族/族裔（SRR）群体的基因混合情况。在此，我们在美国的HIV阳性儿童中，利用跨SRR群体的基因确定祖先（GDA），并研究GDA与HIV-1 RNA及CD4细胞计数之间的关联。
通过实时PCR在994名未接受抗逆转录病毒治疗的HIV阳性儿童中检测了41个用于区分7个大陆地区的AIMs。使用STRUCTURE软件，将每个个体的基因型与来自全球人群的大量参考个体的等位基因频率进行比较，从而估计GDA。计算每个SRR类别的GDA均值。采用线性回归对CD4细胞计数和log10 RNA水平的GDA进行建模，并对SRR和年龄进行校正。
受试者中61%为黑人，25%为西班牙裔，13%为白人，1.3%种族不明。平均年龄为2.3岁（45%为男性），平均CD4细胞计数为每立方毫米981个细胞，平均log10 RNA水平为5.11。所有SRR群体均存在明显的异质性，西班牙裔的基因混合程度较高。在调整后的线性回归模型中，与100%非洲血统的受试者相比，估计100%欧洲血统的受试者log10 RNA水平高0.33（95%置信区间：0.03至0.62，P = 0.028），CD4细胞计数每立方毫米低253个（95%置信区间：-517至11，P = 0.06）。
在美国这一队列HIV感染儿童中发现了明显的大陆基因混合情况。GDA导致了除SRR之外RNA和CD4细胞计数的差异，在与HIV感染相关的结果可能具有遗传成分时应予以考虑。
