The influence of CCL3L1 gene-containing segmental duplications on HIV-1/AIDS susceptibility

被引：865

作者：

Gonzalez, E

Kulkarni, H

Bolivar, H

Mangano, A

Sanchez, R

Catano, G

Nibbs, RJ

Freedman, BI

Quinones, MP

Bamshad, MJ

Murthy, KK

Rovin, BH

Bradley, W

Clark, RA

Anderson, SA

O'Connell, RJ

Agan, BK

Ahuja, SS

Bologna, R

Sen, L

Dolan, MJ

Ahuja, SK

机构：

[1] Univ Texas, Hlth Sci Ctr, Vet Adm Res Ctr AIDS & HIV1 Infect, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA

[2] Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA

[3] Consejo Nacl Invest Cient & Tecn, Lab Biol Celular & Retrovirus, RA-1245 Buenos Aires, DF, Argentina

[4] Hosp Pediat JP Garrahan, Serv Infectol, RA-1245 Buenos Aires, DF, Argentina

[5] Cancer Res UK Beatson Labs, Glasgow G61 1BD, Lanark, Scotland

[6] Wake Forest Univ, Sch Med, Dept Internal Med, Winston Salem, NC 27157 USA

[7] Univ Utah, Dept Human Genet, Salt Lake City, UT 84112 USA

[8] Univ Utah, Dept Pediat, Salt Lake City, UT 84112 USA

[9] SW Fdn Biomed Res, San Antonio, TX 78227 USA

[10] Ohio State Univ, Div Nephrol, Columbus, OH 43210 USA

[11] Wilford Hall USAF Med Ctr, Infect Dis Serv, Lackland AFB, TX 78236 USA

[12] Wilford Hall USAF Med Ctr, Tri Serv AIDS Clin Consortium, Lackland AFB, TX 78236 USA

[13] Wilford Hall USAF Med Ctr, Henry M Jackson Fdn, Lackland AFB, TX 78236 USA

[14] Def Inst Med Operat, Brooks AFB, TX 78235 USA

来源：

SCIENCE | 2005年 / 307卷 / 5714期

关键词：

D O I：

10.1126/science.1101160

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Segmental duplications in the human genome are selectively enriched for genes involved in immunity, although the phenotypic consequences for host defense are unknown. We show that there are significant interindividual and interpopulation differences in the copy number of a segmental duplication encompassing the gene encoding CCL3L1 (MIP-1alphaP), a potent human immunodeficiency virus-1 (HIV-1)-suppressive chemokine and ligand for the HIV coreceptor CCR5. Possession of a CCL3L1 copy number lower than the population average is associated with markedly enhanced HIV/acquired immunodeficiency syndrome (AIDS) susceptibility. This susceptibility is even greater in individuals who also possess disease-accelerating CCR5 genotypes. This relationship between CCL3L1 dose and altered HIV/AIDS susceptibility points to a central role for CCL3L1 in HIV/AIDS pathogenesis and indicates that differences in the dose of immune response genes may constitute a genetic basis for variable responses to infectious diseases.

引用

页码：1434 / 1440

页数：7

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