Contribution of genetic background, traditional risk factors, and HIV-related factors to coronary artery disease events in HIV-positive persons

Margalida Rotger; Tracy R. Glass; Thomas Junier; Jens Lundgren; James D. Neaton; Estella S. Poloni; Angélique B. Van 'T Wout; Rubin Lubomirov; Sara Colombo; Raquel Martinez; Andri Rauch; Huldrych F. Günthard; Jacqueline Neuhaus; Deborah Wentworth; Danielle Van Manen; Luuk A. Gras; Hanneke Schuitemaker; Laura Albini; Carlo Torti; Lisa P. Jacobson; Xiuhong Li; Lawrence A. Kingsley; Federica Carli; Giovanni Guaraldi; Emily S. Ford; Irini Sereti; Colleen Hadigan; Esteban Martinez; Mireia Arnedo; Lander Egaña-Gorroño; Jose M. Gatell; Matthew Law; Courtney Bendall; Kathy Petoumenos; Jürgen Rockstroh; Jan Christian Wasmuth; Kabeya Kabamba; Marc Delforge; Stephane De Wit; Florian Berger; Stefan Mauss; Mariana De Paz Sierra; Marcelo Losso; Waldo H. Belloso; Maria Leyes; Antoni Campins; Annalisa Mondi; Andrea De Luca; Ignacio Bernardino; Mónica Barriuso-Iglesias; Ana Torrecilla-Rodriguez; Juan Gonzalez-Garcia; José R. Arribas; Iuri Fanti; Silvia Gel; Jordi Puig; Eugenia Negredo; Mar Gutierrez; Pere Domingo; Julia Fischer; Gerd Fätkenheuer; Carlos Alonso-Villaverde; Alan MacKen; James Woo; Tara McGinty; Patrick Mallon; Alexandra Mangili; Sally Skinner; Christine A. Wanke; Peter Reiss; Rainer Weber; Heiner C. Bucher; Jacques Fellay; Amalio Telenti; Philip E. Tarr

doi:10.1093/cid/cit196

Contribution of genetic background, traditional risk factors, and HIV-related factors to coronary artery disease events in HIV-positive persons

Margalida Rotger, Tracy R. Glass, Thomas Junier, Jens Lundgren, James D. Neaton, Estella S. Poloni, Angélique B. Van 'T Wout, Rubin Lubomirov, Sara Colombo, Raquel Martinez, Andri Rauch, Huldrych F. Günthard, Jacqueline Neuhaus, Deborah Wentworth, Danielle Van Manen, Luuk A. Gras, Hanneke Schuitemaker, Laura Albini, Carlo Torti, Lisa P. JacobsonXiuhong Li, Lawrence A. Kingsley, Federica Carli, Giovanni Guaraldi, Emily S. Ford, Irini Sereti, Colleen Hadigan, Esteban Martinez, Mireia Arnedo, Lander Egaña-Gorroño, Jose M. Gatell, Matthew Law, Courtney Bendall, Kathy Petoumenos, Jürgen Rockstroh, Jan Christian Wasmuth, Kabeya Kabamba, Marc Delforge, Stephane De Wit, Florian Berger, Stefan Mauss, Mariana De Paz Sierra, Marcelo Losso, Waldo H. Belloso, Maria Leyes, Antoni Campins, Annalisa Mondi, Andrea De Luca, Ignacio Bernardino, Mónica Barriuso-Iglesias, Ana Torrecilla-Rodriguez, Juan Gonzalez-Garcia, José R. Arribas, Iuri Fanti, Silvia Gel, Jordi Puig, Eugenia Negredo, Mar Gutierrez, Pere Domingo, Julia Fischer, Gerd Fätkenheuer, Carlos Alonso-Villaverde, Alan MacKen, James Woo, Tara McGinty, Patrick Mallon, Alexandra Mangili, Sally Skinner, Christine A. Wanke, Peter Reiss, Rainer Weber, Heiner C. Bucher, Jacques Fellay, Amalio Telenti, Philip E. Tarr

Department of Medicine

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

59 Citations (Scopus)

Abstract

Background Persons infected with human immunodeficiency virus (HIV) have increased rates of coronary artery disease (CAD). The relative contribution of genetic background, HIV-related factors, antiretroviral medications, and traditional risk factors to CAD has not been fully evaluated in the setting of HIV infection.Methods In the general population, 23 common single-nucleotide polymorphisms (SNPs) were shown to be associated with CAD through genome-wide association analysis. Using the Metabochip, we genotyped 1875 HIV-positive, white individuals enrolled in 24 HIV observational studies, including 571 participants with a first CAD event during the 9-year study period and 1304 controls matched on sex and cohort.Results A genetic risk score built from 23 CAD-associated SNPs contributed significantly to CAD (P = 2.9×10 -4). In the final multivariable model, participants with an unfavorable genetic background (top genetic score quartile) had a CAD odds ratio (OR) of 1.47 (95% confidence interval [CI], 1.05-2.04). This effect was similar to hypertension (OR = 1.36; 95% CI, 1.06-1.73), hypercholesterolemia (OR = 1.51; 95% CI, 1.16-1.96), diabetes (OR = 1.66; 95% CI, 1.10-2.49), ≥1 year lopinavir exposure (OR = 1.36; 95% CI, 1.06-1.73), and current abacavir treatment (OR = 1.56; 95% CI, 1.17-2.07). The effect of the genetic risk score was additive to the effect of nongenetic CAD risk factors, and did not change after adjustment for family history of CAD.Conclusions In the setting of HIV infection, the effect of an unfavorable genetic background was similar to traditional CAD risk factors and certain adverse antiretroviral exposures. Genetic testing may provide prognostic information complementary to family history of CAD. © 2013 The Author.

Original language	English
Pages (from-to)	112-121
Journal	Clinical Infectious Diseases
Volume	57
Issue number	1
DOIs	https://doi.org/10.1093/cid/cit196
Publication status	Published - 1 Jul 2013

Keywords

antiretroviral therapy
coronary artery disease
genetics
HIV infection
traditional risk factors

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1093/cid/cit196

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Rotger, M., Glass, T. R., Junier, T., Lundgren, J., Neaton, J. D., Poloni, E. S., Van 'T Wout, A. B., Lubomirov, R., Colombo, S., Martinez, R., Rauch, A., Günthard, H. F., Neuhaus, J., Wentworth, D., Van Manen, D., Gras, L. A., Schuitemaker, H., Albini, L., Torti, C., ... Tarr, P. E. (2013). Contribution of genetic background, traditional risk factors, and HIV-related factors to coronary artery disease events in HIV-positive persons. Clinical Infectious Diseases, 57(1), 112-121. https://doi.org/10.1093/cid/cit196

@article{46b21f78796846d0a26fbe2f7c23b169,

title = "Contribution of genetic background, traditional risk factors, and HIV-related factors to coronary artery disease events in HIV-positive persons",

abstract = "Background Persons infected with human immunodeficiency virus (HIV) have increased rates of coronary artery disease (CAD). The relative contribution of genetic background, HIV-related factors, antiretroviral medications, and traditional risk factors to CAD has not been fully evaluated in the setting of HIV infection.Methods In the general population, 23 common single-nucleotide polymorphisms (SNPs) were shown to be associated with CAD through genome-wide association analysis. Using the Metabochip, we genotyped 1875 HIV-positive, white individuals enrolled in 24 HIV observational studies, including 571 participants with a first CAD event during the 9-year study period and 1304 controls matched on sex and cohort.Results A genetic risk score built from 23 CAD-associated SNPs contributed significantly to CAD (P = 2.9×10 -4). In the final multivariable model, participants with an unfavorable genetic background (top genetic score quartile) had a CAD odds ratio (OR) of 1.47 (95% confidence interval [CI], 1.05-2.04). This effect was similar to hypertension (OR = 1.36; 95% CI, 1.06-1.73), hypercholesterolemia (OR = 1.51; 95% CI, 1.16-1.96), diabetes (OR = 1.66; 95% CI, 1.10-2.49), ≥1 year lopinavir exposure (OR = 1.36; 95% CI, 1.06-1.73), and current abacavir treatment (OR = 1.56; 95% CI, 1.17-2.07). The effect of the genetic risk score was additive to the effect of nongenetic CAD risk factors, and did not change after adjustment for family history of CAD.Conclusions In the setting of HIV infection, the effect of an unfavorable genetic background was similar to traditional CAD risk factors and certain adverse antiretroviral exposures. Genetic testing may provide prognostic information complementary to family history of CAD. {\textcopyright} 2013 The Author.",

keywords = "antiretroviral therapy, coronary artery disease, genetics, HIV infection, traditional risk factors",

author = "Margalida Rotger and Glass, {Tracy R.} and Thomas Junier and Jens Lundgren and Neaton, {James D.} and Poloni, {Estella S.} and {Van 'T Wout}, {Ang{\'e}lique B.} and Rubin Lubomirov and Sara Colombo and Raquel Martinez and Andri Rauch and G{\"u}nthard, {Huldrych F.} and Jacqueline Neuhaus and Deborah Wentworth and {Van Manen}, Danielle and Gras, {Luuk A.} and Hanneke Schuitemaker and Laura Albini and Carlo Torti and Jacobson, {Lisa P.} and Xiuhong Li and Kingsley, {Lawrence A.} and Federica Carli and Giovanni Guaraldi and Ford, {Emily S.} and Irini Sereti and Colleen Hadigan and Esteban Martinez and Mireia Arnedo and Lander Ega{\~n}a-Gorro{\~n}o and Gatell, {Jose M.} and Matthew Law and Courtney Bendall and Kathy Petoumenos and J{\"u}rgen Rockstroh and Wasmuth, {Jan Christian} and Kabeya Kabamba and Marc Delforge and {De Wit}, Stephane and Florian Berger and Stefan Mauss and {De Paz Sierra}, Mariana and Marcelo Losso and Belloso, {Waldo H.} and Maria Leyes and Antoni Campins and Annalisa Mondi and {De Luca}, Andrea and Ignacio Bernardino and M{\'o}nica Barriuso-Iglesias and Ana Torrecilla-Rodriguez and Juan Gonzalez-Garcia and Arribas, {Jos{\'e} R.} and Iuri Fanti and Silvia Gel and Jordi Puig and Eugenia Negredo and Mar Gutierrez and Pere Domingo and Julia Fischer and Gerd F{\"a}tkenheuer and Carlos Alonso-Villaverde and Alan MacKen and James Woo and Tara McGinty and Patrick Mallon and Alexandra Mangili and Sally Skinner and Wanke, {Christine A.} and Peter Reiss and Rainer Weber and Bucher, {Heiner C.} and Jacques Fellay and Amalio Telenti and Tarr, {Philip E.}",

year = "2013",

month = jul,

day = "1",

doi = "10.1093/cid/cit196",

language = "English",

volume = "57",

pages = "112--121",

number = "1",

}

Rotger, M, Glass, TR, Junier, T, Lundgren, J, Neaton, JD, Poloni, ES, Van 'T Wout, AB, Lubomirov, R, Colombo, S, Martinez, R, Rauch, A, Günthard, HF, Neuhaus, J, Wentworth, D, Van Manen, D, Gras, LA, Schuitemaker, H, Albini, L, Torti, C, Jacobson, LP, Li, X, Kingsley, LA, Carli, F, Guaraldi, G, Ford, ES, Sereti, I, Hadigan, C, Martinez, E, Arnedo, M, Egaña-Gorroño, L, Gatell, JM, Law, M, Bendall, C, Petoumenos, K, Rockstroh, J, Wasmuth, JC, Kabamba, K, Delforge, M, De Wit, S, Berger, F, Mauss, S, De Paz Sierra, M, Losso, M, Belloso, WH, Leyes, M, Campins, A, Mondi, A, De Luca, A, Bernardino, I, Barriuso-Iglesias, M, Torrecilla-Rodriguez, A, Gonzalez-Garcia, J, Arribas, JR, Fanti, I, Gel, S, Puig, J, Negredo, E, Gutierrez, M, Domingo, P, Fischer, J, Fätkenheuer, G, Alonso-Villaverde, C, MacKen, A, Woo, J, McGinty, T, Mallon, P, Mangili, A, Skinner, S, Wanke, CA, Reiss, P, Weber, R, Bucher, HC, Fellay, J, Telenti, A & Tarr, PE 2013, 'Contribution of genetic background, traditional risk factors, and HIV-related factors to coronary artery disease events in HIV-positive persons', Clinical Infectious Diseases, vol. 57, no. 1, pp. 112-121. https://doi.org/10.1093/cid/cit196

TY - JOUR

T1 - Contribution of genetic background, traditional risk factors, and HIV-related factors to coronary artery disease events in HIV-positive persons

AU - Rotger, Margalida

AU - Glass, Tracy R.

AU - Junier, Thomas

AU - Lundgren, Jens

AU - Neaton, James D.

AU - Poloni, Estella S.

AU - Van 'T Wout, Angélique B.

AU - Lubomirov, Rubin

AU - Colombo, Sara

AU - Martinez, Raquel

AU - Rauch, Andri

AU - Günthard, Huldrych F.

AU - Neuhaus, Jacqueline

AU - Wentworth, Deborah

AU - Van Manen, Danielle

AU - Gras, Luuk A.

AU - Schuitemaker, Hanneke

AU - Albini, Laura

AU - Torti, Carlo

AU - Jacobson, Lisa P.

AU - Li, Xiuhong

AU - Kingsley, Lawrence A.

AU - Carli, Federica

AU - Guaraldi, Giovanni

AU - Ford, Emily S.

AU - Sereti, Irini

AU - Hadigan, Colleen

AU - Martinez, Esteban

AU - Arnedo, Mireia

AU - Egaña-Gorroño, Lander

AU - Gatell, Jose M.

AU - Law, Matthew

AU - Bendall, Courtney

AU - Petoumenos, Kathy

AU - Rockstroh, Jürgen

AU - Wasmuth, Jan Christian

AU - Kabamba, Kabeya

AU - Delforge, Marc

AU - De Wit, Stephane

AU - Berger, Florian

AU - Mauss, Stefan

AU - De Paz Sierra, Mariana

AU - Losso, Marcelo

AU - Belloso, Waldo H.

AU - Leyes, Maria

AU - Campins, Antoni

AU - Mondi, Annalisa

AU - De Luca, Andrea

AU - Bernardino, Ignacio

AU - Barriuso-Iglesias, Mónica

AU - Torrecilla-Rodriguez, Ana

AU - Gonzalez-Garcia, Juan

AU - Arribas, José R.

AU - Fanti, Iuri

AU - Gel, Silvia

AU - Puig, Jordi

AU - Negredo, Eugenia

AU - Gutierrez, Mar

AU - Domingo, Pere

AU - Fischer, Julia

AU - Fätkenheuer, Gerd

AU - Alonso-Villaverde, Carlos

AU - MacKen, Alan

AU - Woo, James

AU - McGinty, Tara

AU - Mallon, Patrick

AU - Mangili, Alexandra

AU - Skinner, Sally

AU - Wanke, Christine A.

AU - Reiss, Peter

AU - Weber, Rainer

AU - Bucher, Heiner C.

AU - Fellay, Jacques

AU - Telenti, Amalio

AU - Tarr, Philip E.

PY - 2013/7/1

Y1 - 2013/7/1

N2 - Background Persons infected with human immunodeficiency virus (HIV) have increased rates of coronary artery disease (CAD). The relative contribution of genetic background, HIV-related factors, antiretroviral medications, and traditional risk factors to CAD has not been fully evaluated in the setting of HIV infection.Methods In the general population, 23 common single-nucleotide polymorphisms (SNPs) were shown to be associated with CAD through genome-wide association analysis. Using the Metabochip, we genotyped 1875 HIV-positive, white individuals enrolled in 24 HIV observational studies, including 571 participants with a first CAD event during the 9-year study period and 1304 controls matched on sex and cohort.Results A genetic risk score built from 23 CAD-associated SNPs contributed significantly to CAD (P = 2.9×10 -4). In the final multivariable model, participants with an unfavorable genetic background (top genetic score quartile) had a CAD odds ratio (OR) of 1.47 (95% confidence interval [CI], 1.05-2.04). This effect was similar to hypertension (OR = 1.36; 95% CI, 1.06-1.73), hypercholesterolemia (OR = 1.51; 95% CI, 1.16-1.96), diabetes (OR = 1.66; 95% CI, 1.10-2.49), ≥1 year lopinavir exposure (OR = 1.36; 95% CI, 1.06-1.73), and current abacavir treatment (OR = 1.56; 95% CI, 1.17-2.07). The effect of the genetic risk score was additive to the effect of nongenetic CAD risk factors, and did not change after adjustment for family history of CAD.Conclusions In the setting of HIV infection, the effect of an unfavorable genetic background was similar to traditional CAD risk factors and certain adverse antiretroviral exposures. Genetic testing may provide prognostic information complementary to family history of CAD. © 2013 The Author.

AB - Background Persons infected with human immunodeficiency virus (HIV) have increased rates of coronary artery disease (CAD). The relative contribution of genetic background, HIV-related factors, antiretroviral medications, and traditional risk factors to CAD has not been fully evaluated in the setting of HIV infection.Methods In the general population, 23 common single-nucleotide polymorphisms (SNPs) were shown to be associated with CAD through genome-wide association analysis. Using the Metabochip, we genotyped 1875 HIV-positive, white individuals enrolled in 24 HIV observational studies, including 571 participants with a first CAD event during the 9-year study period and 1304 controls matched on sex and cohort.Results A genetic risk score built from 23 CAD-associated SNPs contributed significantly to CAD (P = 2.9×10 -4). In the final multivariable model, participants with an unfavorable genetic background (top genetic score quartile) had a CAD odds ratio (OR) of 1.47 (95% confidence interval [CI], 1.05-2.04). This effect was similar to hypertension (OR = 1.36; 95% CI, 1.06-1.73), hypercholesterolemia (OR = 1.51; 95% CI, 1.16-1.96), diabetes (OR = 1.66; 95% CI, 1.10-2.49), ≥1 year lopinavir exposure (OR = 1.36; 95% CI, 1.06-1.73), and current abacavir treatment (OR = 1.56; 95% CI, 1.17-2.07). The effect of the genetic risk score was additive to the effect of nongenetic CAD risk factors, and did not change after adjustment for family history of CAD.Conclusions In the setting of HIV infection, the effect of an unfavorable genetic background was similar to traditional CAD risk factors and certain adverse antiretroviral exposures. Genetic testing may provide prognostic information complementary to family history of CAD. © 2013 The Author.

KW - antiretroviral therapy

KW - coronary artery disease

KW - genetics

KW - HIV infection

KW - traditional risk factors

U2 - 10.1093/cid/cit196

DO - 10.1093/cid/cit196

M3 - Article

VL - 57

SP - 112

EP - 121

IS - 1

ER -

Contribution of genetic background, traditional risk factors, and HIV-related factors to coronary artery disease events in HIV-positive persons

Abstract

Keywords

UN SDGs

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