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; MAGNIFICENT Consortium

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, MAGNIFICENT Consortium

61 Citationer (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.

Originalsprog	Engelsk
Tidsskrift	Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Vol/bind	57
Udgave nummer	1
Sider (fra-til)	112-21
Antal sider	10
ISSN	1058-4838
DOI	https://doi.org/10.1093/cid/cit196
Status	Udgivet - jul. 2013

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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., ... MAGNIFICENT Consortium (2013). Contribution of genetic background, traditional risk factors, and HIV-related factors to coronary artery disease events in HIV-positive persons. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 57(1), 112-21. https://doi.org/10.1093/cid/cit196

Contribution of genetic background, traditional risk factors, and HIV-related factors to coronary artery disease events in HIV-positive persons. / Rotger, Margalida; Glass, Tracy R; Junier, Thomas et al.
I: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, Bind 57, Nr. 1, 07.2013, s. 112-21.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

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, J-C, 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 & MAGNIFICENT Consortium 2013, 'Contribution of genetic background, traditional risk factors, and HIV-related factors to coronary artery disease events in HIV-positive persons', Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, bind 57, nr. 1, s. 112-21. https://doi.org/10.1093/cid/cit196

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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.",

keywords = "Adolescent, Adult, Aged, Aged, 80 and over, Coronary Artery Disease, Female, Genetic Predisposition to Disease, HIV Infections, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors, Young Adult",

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 Jan-Christian Wasmuth 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 {MAGNIFICENT Consortium}",

year = "2013",

month = jul,

doi = "10.1093/cid/cit196",

language = "English",

volume = "57",

pages = "112--21",

journal = "Clinical infectious diseases : an official publication of the Infectious Diseases Society of America",

issn = "1058-4838",

publisher = "Oxford University Press",

number = "1",

}

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 - MAGNIFICENT Consortium

PY - 2013/7

Y1 - 2013/7

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.

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.

KW - Adolescent

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Coronary Artery Disease

KW - Female

KW - Genetic Predisposition to Disease

KW - HIV Infections

KW - Humans

KW - Male

KW - Middle Aged

KW - Polymorphism, Single Nucleotide

KW - Risk Factors

KW - Young Adult

U2 - 10.1093/cid/cit196

DO - 10.1093/cid/cit196

M3 - Journal article

C2 - 23532479

SN - 1058-4838

VL - 57

SP - 112

EP - 121

JO - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

JF - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

IS - 1

ER -

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

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