Nuffield Department of Medicine, Oxford University, UK.
Biomedical Research and Training Institute, Zimbabwe.
AIDS. 2021 Dec 1;35(15):2445-2450. doi: 10.1097/QAD.0000000000003053.
Untreated perinatal HIV-1 infection is often associated with rapid disease progression in children with HIV (CWH), characterized by high viral loads and early mortality. TRIM22 is a host restriction factor, which directly inhibits HIV-1 transcription, and its genotype variation is associated with disease progression in adults. We tested the hypothesis that TRIM22 genotype is associated with disease progression in CWH.
ART-naive CWH, aged 6-16 years, were recruited from primary care clinics in Harare, Zimbabwe. We performed a candidate gene association study of TRIM22 genotype and haplotypes with markers of disease progression and indicators of advanced disease.
TRIM22 exons three and four were sequenced by Sanger sequencing and single nucleotide polymorphisms were associated with markers of disease progression (CD4+ T-cell count and HIV viral load) and clinical indicators of advanced HIV disease (presence of stunting and chronic diarrhoea). Associations were tested using multivariate linear and logistic regression models.
A total of 241 children, median age 11.4 years, 50% female, were included. Stunting was present in 16% of participants. Five SNPs were analyzed including rs7935564, rs2291842, rs78484876, rs1063303 and rs61735273. The median CD4+ count was 342 (IQR: 195-533) cells/μl and median HIV-1 viral load 34 199 (IQR: 8211-90 662) IU/ml. TRIM22 genotype and haplotypes were not associated with CD4+ T-cell count, HIV-1 viral load, stunting or chronic diarrhoea.
TRIM22 genotype was not associated with markers of HIV disease progression markers or advanced disease in CWH.
未经治疗的围产期 HIV-1 感染常与 HIV 儿童(CWH)的疾病快速进展相关,其特征为病毒载量高和早期死亡率高。TRIM22 是一种宿主限制因子,可直接抑制 HIV-1 转录,其基因型变异与成人疾病进展相关。我们检验了 TRIM22 基因型与 CWH 疾病进展相关的假设。
来自津巴布韦哈拉雷初级保健诊所的 6-16 岁未经 ART 治疗的 CWH 参与了此次候选基因关联研究。我们对 TRIM22 基因型和单倍型与疾病进展标志物和晚期疾病指标进行了关联分析。
通过 Sanger 测序对 TRIM22 外显子 3 和 4 进行测序,单核苷酸多态性与疾病进展标志物(CD4+ T 细胞计数和 HIV 病毒载量)和晚期 HIV 疾病的临床指标(存在发育迟缓及慢性腹泻)相关联。使用多元线性和逻辑回归模型检验关联。
共纳入 241 名儿童,中位年龄 11.4 岁,50%为女性,16%存在发育迟缓。分析了 5 个单核苷酸多态性,包括 rs7935564、rs2291842、rs78484876、rs1063303 和 rs61735273。CD4+计数中位数为 342(IQR:195-533)个/μl,HIV-1 病毒载量中位数为 34199(IQR:8211-90662)IU/ml。TRIM22 基因型和单倍型与 CD4+ T 细胞计数、HIV-1 病毒载量、发育迟缓或慢性腹泻无关。
TRIM22 基因型与 CWH 的 HIV 疾病进展标志物或晚期疾病无关。