Protective effect of CCR5 delta 32 heterozygosity is restricted by SDF-1 genotype in children with HIV-1 infection.
Protective effect of CCR5 delta 32 heterozygosity is restricted by SDF-1 genotype in children with HIV-1 infection.
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CCR5 delta 32 杂合性对 HIV-1 感染儿童的保护作用受到 SDF-1 基因型的限制。
DOI：
10.1097/00002030-200107270-00003
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发表时间：
2001
期刊：
影响因子：
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通讯作者：
Venzon,DJ
中科院分区：
文献类型：
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作者：
Sei,S;Boler,AM;Nguyen,GT;Stewart,SK;Yang,QE;Edgerly,M;Wood,LV;Brouwers,P;Venzon,DJ
目的探讨cc趋化因子受体5基因（CCR5 wt/Δ32） 32个碱基对杂合缺失和基质细胞源性因子-1β基因转录物（SDF1-3 ‘ a） 3 ’非翻译区常见多态性对儿童艾滋病的影响。设计根据CCR5和SDF-1基因型比较127例（58例白种人、60例非裔美国人和9例西班牙裔）围产期HIV-1感染儿童的HIV-1疾病进展率和病毒负担。结果：无论种族背景如何，CCR5 wt/Δ32基因型与感染前5年艾滋病感染并发症的延迟发作相关[相对危险度(RH)= 0.22；95%置信区间（CI）， 0.012-1.02；P = 0.053)。同样地，CCR5 wt/Δ32对严重免疫抑制和HIV-1脑病具有早期保护作用，但仅适用于没有SDF1-3 ' A的患者（RH= 0; 95% CI, 0 - 0.70； P= 0.020， RH= 0; 95% CI, 0 - 0.71； P= 0.021）。在5岁前（n= 81）进行检查时，CCR5 wt/Δ32患儿的细胞相关HIV-1 DNA水平明显低于野生型纯合子（P= 0.016，按种族调整），而SDF1-3 ' A携带者的水平相对较高（P= 0.047，按种族调整）。虽然CCR5 wt/Δ32的抗病延缓作用随后消失，但不含SDF1-3′A的CCR5 Δ32杂合子的死亡时间仍显著延迟（RH= 0; 95% CI, 0 - 0.53； P= 0.008）。结论在儿童艾滋病中，CCR5 wt/Δ32的保护作用在感染早期更为明显，似乎被SDF1-3 ' A基因型所消除。
ObjectiveTo determine the influences on pediatric AIDS of a heterozygous 32 base pair deletion in the CC-chemokine receptor 5 gene (CCR5 wt/Δ32) and a common polymorphism in the 3′ untranslated region of stromal cell-derived factor-1β gene transcript (SDF1-3′ A).DesignThe rate of HIV-1 disease progression and viral burden were compared according to the CCR5 and SDF-1 genotypes in 127 (58 Caucasians, 60 African-Americans and nine Hispanics) perinatally HIV-1-infected children.ResultsRegardless of ethnic background, the CCR5 wt/Δ32 genotype was associated with a delayed onset of AIDS-defining infectious complications during the first 5 years of infection [relative hazard (RH)= 0.22; 95% confidence interval (CI), 0.012–1.02; P= 0.053]. Similarly, CCR5 wt/Δ32 conferred an early protection against severe immune suppression and HIV-1 encephalopathy, but only in those without SDF1-3′ A (RH= 0; 95% CI, 0–0.70; P= 0.020, and RH= 0; 95% CI, 0–0.71; P= 0.021, respectively). When examined before 5 years of age (n= 81), the children with CCR5 wt/Δ32 had significantly lower levels of cell-associated HIV-1 DNA than wild-type homozygotes (P= 0.016, adjusted by race), while SDF1-3′ A carriers had relatively higher levels (P= 0.047, adjusted by race). Although the disease-retarding effect of CCR5 wt/Δ32 subsequently disappeared, time to death was still significantly delayed in the CCR5 Δ32 heterozygotes without SDF1-3′ A (RH= 0; 95% CI, 0–0.53; P= 0.008).ConclusionIn pediatric AIDS, the protective effect of CCR5 wt/Δ32 is more pronounced in early years of infection and appears to be abrogated by the SDF1-3′ A genotype.