Race-specific HIV-1 disease-modifying effects associated with CCR5 haplotypes

Enrique Gonzalez; Mike Bamshad; Naoko Sato; Srinivas Mummidi; Rahul Dhanda; Gabriel Catano; Sonia Cabrera; Megan McBride; Xuan Hien Cao; Gerald Merrill; Peter O'Connell; Donald W. Bowden; Barry I. Freedman; Stephanie A. Anderson; Elizabeth A. Walter; James S. Evans; Kevin T. Stephan; Robert A. Clark; Sanjay Tyagi; Seema S. Ahuja; Matthew J. Dolan; Sunil K. Ahuja

doi:10.1073/pnas.96.21.12004

Race-specific HIV-1 disease-modifying effects associated with CCR5 haplotypes

Enrique Gonzalez, Mike Bamshad, Naoko Sato, Srinivas Mummidi, Rahul Dhanda, Gabriel Catano, Sonia Cabrera, Megan McBride, Xuan Hien Cao, Gerald Merrill, Peter O'Connell, Donald W. Bowden, Barry I. Freedman, Stephanie A. Anderson, Elizabeth A. Walter, James S. Evans, Kevin T. Stephan, Robert A. Clark, Sanjay Tyagi, Seema S. AhujaMatthew J. Dolan, Sunil K. Ahuja^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

230 Scopus citations

Abstract

Genetic variation in CC chemokine receptor 5 (CCR5), the major HIV-1 coreceptor, has been shown to influence HIV-1 transmission and disease progression. However, it is generally assumed that the same CCR5 genotype (or haplotype) has similar phenotypic effects in different populations. To test this assumption, we used an evolutionary-based classification of CCR5 haplotypes to determine their associated HIV-1 disease-modifying effects in a large well-characterized racially mixed cohort of HIV-1-seropositive individuals. We demonstrate that the spectrum of CCR5 haplotypes associated with disease acceleration or retardation differs between African Americans and Caucasians. Also, we show that there is a strong interactive effect between CCR5 haplotypes with different evolutionary histories. The striking population-specific phenotypic effects associated with CCR5 haplotypes emphasize the importance of understanding the evolutionary context in which disease susceptibility genes are expressed.

Original language	English
Pages (from-to)	12004-12009
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	96
Issue number	21
DOIs	https://doi.org/10.1073/pnas.96.21.12004
State	Published - 12 Oct 1999
Externally published	Yes

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Gonzalez, E., Bamshad, M., Sato, N., Mummidi, S., Dhanda, R., Catano, G., Cabrera, S., McBride, M., Cao, X. H., Merrill, G., O'Connell, P., Bowden, D. W., Freedman, B. I., Anderson, S. A., Walter, E. A., Evans, J. S., Stephan, K. T., Clark, R. A., Tyagi, S., ... Ahuja, S. K. (1999). Race-specific HIV-1 disease-modifying effects associated with CCR5 haplotypes. Proceedings of the National Academy of Sciences of the United States of America, 96(21), 12004-12009. https://doi.org/10.1073/pnas.96.21.12004

@article{1d174868c32a493c9c5350eb48a96ff1,

title = "Race-specific HIV-1 disease-modifying effects associated with CCR5 haplotypes",

abstract = "Genetic variation in CC chemokine receptor 5 (CCR5), the major HIV-1 coreceptor, has been shown to influence HIV-1 transmission and disease progression. However, it is generally assumed that the same CCR5 genotype (or haplotype) has similar phenotypic effects in different populations. To test this assumption, we used an evolutionary-based classification of CCR5 haplotypes to determine their associated HIV-1 disease-modifying effects in a large well-characterized racially mixed cohort of HIV-1-seropositive individuals. We demonstrate that the spectrum of CCR5 haplotypes associated with disease acceleration or retardation differs between African Americans and Caucasians. Also, we show that there is a strong interactive effect between CCR5 haplotypes with different evolutionary histories. The striking population-specific phenotypic effects associated with CCR5 haplotypes emphasize the importance of understanding the evolutionary context in which disease susceptibility genes are expressed.",

author = "Enrique Gonzalez and Mike Bamshad and Naoko Sato and Srinivas Mummidi and Rahul Dhanda and Gabriel Catano and Sonia Cabrera and Megan McBride and Cao, {Xuan Hien} and Gerald Merrill and Peter O'Connell and Bowden, {Donald W.} and Freedman, {Barry I.} and Anderson, {Stephanie A.} and Walter, {Elizabeth A.} and Evans, {James S.} and Stephan, {Kevin T.} and Clark, {Robert A.} and Sanjay Tyagi and Ahuja, {Seema S.} and Dolan, {Matthew J.} and Ahuja, {Sunil K.}",

year = "1999",

month = oct,

day = "12",

doi = "10.1073/pnas.96.21.12004",

language = "English",

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Gonzalez, E, Bamshad, M, Sato, N, Mummidi, S, Dhanda, R, Catano, G, Cabrera, S, McBride, M, Cao, XH, Merrill, G, O'Connell, P, Bowden, DW, Freedman, BI, Anderson, SA, Walter, EA, Evans, JS, Stephan, KT, Clark, RA, Tyagi, S, Ahuja, SS, Dolan, MJ & Ahuja, SK 1999, 'Race-specific HIV-1 disease-modifying effects associated with CCR5 haplotypes', Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 21, pp. 12004-12009. https://doi.org/10.1073/pnas.96.21.12004

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T1 - Race-specific HIV-1 disease-modifying effects associated with CCR5 haplotypes

AU - Gonzalez, Enrique

AU - Bamshad, Mike

AU - Sato, Naoko

AU - Mummidi, Srinivas

AU - Dhanda, Rahul

AU - Catano, Gabriel

AU - Cabrera, Sonia

AU - McBride, Megan

AU - Cao, Xuan Hien

AU - Merrill, Gerald

AU - O'Connell, Peter

AU - Bowden, Donald W.

AU - Freedman, Barry I.

AU - Anderson, Stephanie A.

AU - Walter, Elizabeth A.

AU - Evans, James S.

AU - Stephan, Kevin T.

AU - Clark, Robert A.

AU - Tyagi, Sanjay

AU - Ahuja, Seema S.

AU - Dolan, Matthew J.

AU - Ahuja, Sunil K.

PY - 1999/10/12

Y1 - 1999/10/12

N2 - Genetic variation in CC chemokine receptor 5 (CCR5), the major HIV-1 coreceptor, has been shown to influence HIV-1 transmission and disease progression. However, it is generally assumed that the same CCR5 genotype (or haplotype) has similar phenotypic effects in different populations. To test this assumption, we used an evolutionary-based classification of CCR5 haplotypes to determine their associated HIV-1 disease-modifying effects in a large well-characterized racially mixed cohort of HIV-1-seropositive individuals. We demonstrate that the spectrum of CCR5 haplotypes associated with disease acceleration or retardation differs between African Americans and Caucasians. Also, we show that there is a strong interactive effect between CCR5 haplotypes with different evolutionary histories. The striking population-specific phenotypic effects associated with CCR5 haplotypes emphasize the importance of understanding the evolutionary context in which disease susceptibility genes are expressed.

AB - Genetic variation in CC chemokine receptor 5 (CCR5), the major HIV-1 coreceptor, has been shown to influence HIV-1 transmission and disease progression. However, it is generally assumed that the same CCR5 genotype (or haplotype) has similar phenotypic effects in different populations. To test this assumption, we used an evolutionary-based classification of CCR5 haplotypes to determine their associated HIV-1 disease-modifying effects in a large well-characterized racially mixed cohort of HIV-1-seropositive individuals. We demonstrate that the spectrum of CCR5 haplotypes associated with disease acceleration or retardation differs between African Americans and Caucasians. Also, we show that there is a strong interactive effect between CCR5 haplotypes with different evolutionary histories. The striking population-specific phenotypic effects associated with CCR5 haplotypes emphasize the importance of understanding the evolutionary context in which disease susceptibility genes are expressed.

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JF - Proceedings of the National Academy of Sciences of the United States of America

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Race-specific HIV-1 disease-modifying effects associated with CCR5 haplotypes

Abstract

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