宿主病毒复制周期基因中的变异与非洲异性恋 HIV-1 的获得有关。

Variants in host viral replication cycle genes are associated with heterosexual HIV-1 acquisition in Africans.

机构信息

*Department of Anthropology, University of Michigan, Ann Arbor, MI; Departments of †Global Health; ‡Epidemiology; §Medicine, University of Washington, Seattle, WA; ‖Perinatal HIV Research Unit, University of Witwatersrand, Johannesburg, South Africa; ¶Department of Medicine, University of Manitoba, Winnipeg, Canada; #Department of Obstetrics and Gynaecology, University of Nairobi, Nairobi, Kenya; Departments of **Pediatrics; ††Genome Sciences; ‡‡Laboratory Medicine, University of Washington, Seattle, WA; and §§Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA.

出版信息

J Acquir Immune Defic Syndr. 2014 Jun 1;66(2):127-34. doi: 10.1097/QAI.0000000000000113.

DOI:10.1097/QAI.0000000000000113

PMID:24463784

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4025588/

Abstract

OBJECTIVE

We evaluated genetic variants in 51 candidate genes encoding proteins that interact with HIV-1 during the virus life cycle for association with HIV-1 outcomes in an African cohort.

METHODS

Using a nested case-control study within a cohort of heterosexual HIV-1-serodiscordant couples, we genotyped 475 haplotype-tagging single-nucleotide polymorphisms (tagSNPs) and 18 SNPs previously associated with HIV-1 transmission and/or progression (candidate SNPs) in 51 host genes. We used logistic and Cox proportional hazard regression with adjustment for sex, age, and population stratification to detect SNP associations with HIV-1 acquisition, plasma HIV-1 set point, and a composite measure of HIV-1 disease progression. Significant thresholds for tagSNP, but not candidate SNP, associations were subjected to Bonferroni correction for multiple testing.

RESULTS

We evaluated 491 HIV-1-infected and 335 HIV-1-uninfected individuals for 493 SNPs, 459 of which passed quality control filters. Candidate SNP PPIA rs8177826 and tagSNP SMARCB1 rs6003904 were significantly associated with HIV-1 acquisition risk (odds ratio = 0.14, P = 0.03, and odds ratio = 2.11, Pcorr = 0.01, respectively). Furthermore, the TT genotype for CCR5 rs1799988 was associated with a mean 0.2 log10 copies per milliliter lower plasma HIV-1 RNA set point (P = 0.04). We also identified significant associations with HIV-1 disease progression for variants in FUT2 and MBL2.

CONCLUSIONS

Using a targeted gene approach, we identified variants in host genes whose protein products interact with HIV-1 during the virus replication cycle and were associated with HIV-1 outcomes in this African cohort.

摘要

目的

我们评估了 51 个候选基因中编码与 HIV-1 病毒生命周期相互作用的蛋白质的遗传变异，以研究其与非洲队列中 HIV-1 结局的关联。

方法

在异性恋 HIV-1 血清学不一致的夫妇队列中，我们采用嵌套病例对照研究，对 51 个宿主基因中的 475 个单核苷酸多态性（tagSNP）和 18 个先前与 HIV-1 传播和/或进展相关的单核苷酸多态性（候选 SNP）进行基因分型。我们使用逻辑回归和 Cox 比例风险回归，调整性别、年龄和人群分层因素，以检测 SNP 与 HIV-1 获得、血浆 HIV-1 设定点和 HIV-1 疾病进展综合指标的关联。对 tagSNP 显著关联进行了 Bonferroni 校正，以控制多重检验。

结果

我们对 491 名 HIV-1 感染者和 335 名 HIV-1 未感染者进行了 493 个 SNP 的评估，其中 459 个 SNP 通过了质量控制筛选。候选 SNP PPIA rs8177826 和 tagSNP SMARCB1 rs6003904 与 HIV-1 获得风险显著相关（比值比=0.14，P=0.03 和比值比=2.11，Pcorr=0.01）。此外，CCR5 rs1799988 的 TT 基因型与血浆 HIV-1 RNA 设定点平均低 0.2 log10 拷贝/毫升相关（P=0.04）。我们还发现 FUT2 和 MBL2 中的变异与 HIV-1 疾病进展显著相关。