Genetic polymorphism in CX3CR1 and risk of HIV disease.
Genetic polymorphism in CX3CR1 and risk of HIV disease.
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CX3CR1 基因多态性与 HIV 疾病风险。
DOI：
10.1126/science.290.5499.2031a
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Murphy,PM
中科院分区：
文献类型：
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作者：
McDermott,DH;Colla,JS;Kleeberger,CA;Plankey,M;Rosenberg,PS;Smith,ED;Zimmerman,PA;Combadière,C;Leitman,SF;Kaslow,RA;Goedert,JJ;Berger,EA;O'Brien,TR;Murphy,PM
Faure等人(1)报道，在法国白种人HIV队列研究中，趋化因子受体/HIV副受体CX3CR1的等位基因M280与HIV感染风险增加和HIV疾病进展加速相关。在血清转换者（SEROCO）队列中，M280等位基因纯合者（n 16）与参考等位基因T280纯合者（n 306; P 0.039）相比，患艾滋病的相对危险度（RR）为2.13。在SEROCO，标准进展（IMMUNOCO）和长期无症状（ALT）队列中，纯合子M280(2)与HIV感染的相关性显著，P为0.045。在这里，我们报告说，我们无法在三个北美HIV-1感染者队列中证实这些关联：DC同性恋队列（DCG）、同性恋男性多中心艾滋病队列研究（MACS）和多中心血友病队列研究（MHCS）。等位基因M280具有两个非同义单核苷酸多态性（snp），导致异亮氨酸(I)取代了密码子249上的缬氨酸(V)，蛋氨酸(M)取代了密码子280上的苏氨酸(T)。这些snp形成了另外三个可能的等位基因：V249 T280、V249 M280和I249 T280。没有观察到V249 M280，这表明连杆完全不平衡；因此，为了与Faure等人(1)先前使用的命名法一致，我们将该等位基因称为M280。V249 T280是所有种族群体中最常见的等位基因（数据未显示），并且在来自北美的高加索随机献血者中频率相似，为72.2%(3,4)，而来自法国的则为74.3%(1)。20.2%的北美高加索随机献血者携带M280等位基因，而法国为13.5%；7.7%的北美高加索随机献血者携带I249 T280等位基因，而法国为12.2%。基因型在每个种族群体中都处于Hardy-Weinberg平衡，这表明这些等位基因缺乏选择压力。暴露但未感染（n 109）和感染HIV-1 （n 573）的高加索MACS参与者在任何化合物CX3CR1基因型（P 0.72）或等位基因（P 0.82）的分布上没有观察到显著差异，这一发现不能支持CX3CR1在同性恋男性艾滋病毒传播中的作用。使用Cox比例风险模型（PROC PHREG, SAS Institute, Cary， NC），艾滋病进展率和全因死亡率在个体或组合中无显著差异
Faure et al.(1) reported that allele M280 of the chemokine receptor/HIV coreceptor CX3CR1 is associated with both increased risk of HIV infection and accelerated HIV disease progression in studies of Caucasian HIV cohorts from France. In the seroconverters (SEROCO) cohort, the relative risk (RR) for AIDS was 2.13 for those homozygous for the M280 allele (n 16) compared with those homozygous for the reference allele T280 (n 306; P 0.039). In the SEROCO, standard progressor (IMMUNOCO), and long-term asymptomatic (ALT) cohorts, association of homozygous M280 (2) with HIV infection was significant at P 0.045. Here we report that we were unable to confirm these associations in three North American (NA) cohorts of HIV-1 seroconverters: the DC Gay cohort (DCG), the Multicenter AIDS Cohort Study of homosexual men (MACS), and the Multicenter Hemophilia Cohort Study (MHCS). Allele M280 has two nonsynonymous single nucleotide polymorphisms (SNPs), causing substitution of isoleucine (I) for valine (V) at codon 249 and methionine (M) for threonine (T) at codon 280. Three other possible alleles are formed by these SNPs: V249 T280, V249 M280, and I249 T280. V249 M280 has not been observed, an indication of complete linkage disequilibrium; for that reason, and to conform with the nomenclature previously used by Faure et al.(1), we refer to this allele as M280. V249 T280 was the most common allele in all racial groups (data not shown) and was similar in frequency between Caucasian random blood donors from North America, at 72.2%(3, 4), and those from France, at 74.3%(1). Allele M280 was present in 20.2% of NA Caucasian random blood donors, compared with 13.5% of those in France, and 7.7% of NA Caucasian random blood donors possessed I249 T280, compared with 12.2% from France. Genotypes were in Hardy-Weinberg equilibrium within each racial group, which suggests a lack of selective pressure on these alleles. No significant difference was observed between exposed but uninfected (n 109) and HIV-1–infected (n 573) Caucasian MACS participants in the distribution of any compound CX3CR1 genotype (P 0.72) or allele (P 0.82), a finding that fails to support a role for CX3CR1 in HIV transmission among homosexual men. Using a Cox proportional hazards model (PROC PHREG, SAS Institute, Cary, NC), progression rates to AIDS and all-cause mortality were not significantly different in individual or combined