CCR2-64I allele and genotype association with delayed AIDS progression in African women
CCR2-64I allele and genotype association with delayed AIDS progression in African women
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DOI：
10.1016/s0140-6736(05)77688-1
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发表时间：
1998-05-30
期刊：
影响因子：
168.9
通讯作者：
Rowland-Jones, SL
中科院分区：
文献类型：
--
作者：
Anzala, AO;Ball, TB;Rowland-Jones, SL
RESEARCH LETTERS of mother-to-child HIV-transmission, over twice that reported in whites (F= 0· 10). 1 Survival analysis was not done because many CSWs were seropositive on study entry: therefore the results are presented as a defined-disease category analysis, where the cohort is arbitarily partitioned into rapid progressors (RP, who develop AIDS within 4 years of seroconversion), slow progressors (SP, who avoid AIDS for at least 12 years from study entry), and seropositive controls from the rest of the cohort outside the RP/SP categories or of undetermined status (AIDS here is the development of an AIDS defining-illness according to the 1987 CDC definition). The protective CCR2 allele (CCR2-64I) and genotype (CCR2+/64I and 64I/64I) frequencies were significantly elevated among SPs compared to RPs and controls (p= 0· 005 and p= 0· 14, respectively)(table). The CCR2 protective genotypes were three times more frequent among SPs, with a relative risk (RR) of 4· 17: the degree of genotypic discordance between slow and rapid progressors is twice as large as that previously reported in white cohorts, divided into the same disease categories (TT 2· 05). 1 An estimated 21% of SPs (attributable risk, AR) are accounted for by CCR2 genotype-associated protection, compared with 9% in Caucasians: these figures rise to 46% and 42% respectively if the patients who do not fall into either slow or rapid progression categories are removed. Seven SP women had CD4+ T-cell counts in the normal range (> 500/µL); three are CCR2-64I/64I homozygotes. In contrast, no homozygotes for the SDF-1 3'UTR mutation were detected amongst the SP group. Four women were heterozygotes for SDF-1+/31A, but this genotype does not have any protective effect. 2Rapid progression to AIDS is a striking feature of the Nairobi CSW cohort, with a median time to AIDS less than a third that seen in European and North American cohorts. Between 21% and 46% of the survival of women who have not developed AIDS more than 12 years after HIV-1 infection can be attributed to possession of one or two protective CCR2-64I alleles. Although additional undiscovered factors may contribute to this rapid disease progression, it is plausible that the absence of the CCR5 and SDF-1 protective alleles found in white people is partly responsible. As further host-gene polymorphisms which influence HIV-1 susceptibility and disease progression are identified, it will be important to examine their impact in
