Contribution of Genetic Background, Traditional Risk Factors, and HIV-Related Factors to Coronary Artery Disease Events in HIV-Positive Persons

M Rotger; TR Glass; T Junier; J Lundgren; JD Neaton; ES Poloni; AB van 't Wout; R Lubomirov; S Colombo; R Martinez; Andri Rauch; HF Gunthard; J Neuhaus; D Wentworth; D van Manen; LA Gras; H Schuitemaker; L Albini; C Torti; LP Jacobson; XH Li; LA Kingsley; F Carli; G Guaraldi; ES Ford; I Sereti; C Hadigan; E Martinez; M Arnedo; L Egana-Gorrono; JM Gatell; M Law; C Bendall; K Petoumenos; J Rockstroh; JC Wasmuth; K Kabamba; M Delforge; S de Wit; F Berger; S Mauss; MD Sierra; M Losso; WH Belloso; M Leyes; A Campins; A Mondi; A Luca; I Bernardino; M Barriuso-Iglesias; A Torrecilla-Rodriguez; J Gonzalez-Garcia; JR Arribas; I Fanti; S Gel; J Puig; E Negredo; M Gutierrez; P Domingo; J Fischer; G Fatkenheuer; C Alonso-Villaverde; A Macken; J Woo; T McGinty; P Mallon; A Mangili; S Skinner; CA Wanke; P Reiss; R Weber; HC Bucher; J Fellay; A Telenti; PE 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

M Rotger, TR Glass, T Junier, J Lundgren, JD Neaton, ES Poloni, AB van 't Wout, R Lubomirov, S Colombo, R Martinez, Andri Rauch, HF Gunthard, J Neuhaus, D Wentworth, D van Manen, LA Gras, H Schuitemaker, L Albini, C Torti, LP JacobsonXH Li, LA Kingsley, F Carli, G Guaraldi, ES Ford, I Sereti, C Hadigan, E Martinez, M Arnedo, L Egana-Gorrono, JM Gatell, M Law, C Bendall, K Petoumenos, J Rockstroh, JC Wasmuth, K Kabamba, M Delforge, S de Wit, F Berger, S Mauss, MD Sierra, M Losso, WH Belloso, M Leyes, A Campins, A Mondi, A Luca, I Bernardino, M Barriuso-Iglesias, A Torrecilla-Rodriguez, J Gonzalez-Garcia, JR Arribas, I Fanti, S Gel, J Puig, E Negredo, M Gutierrez, P Domingo, J Fischer, G Fatkenheuer, C Alonso-Villaverde, A Macken, J Woo, T McGinty, P Mallon, A Mangili, S Skinner, CA Wanke, P Reiss, R Weber, HC Bucher, J Fellay, A Telenti, PE Tarr

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

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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 = 2.9x10(-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 exposur 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.

Original language	Undefined/Unknown
Pages (from-to)	112-121
Number of pages	10
Journal	Clinical Infectious Diseases
Volume	57
Issue number	1
DOIs	https://doi.org/10.1093/cid/cit196
Publication status	Published - 2013
Externally published	Yes

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10.1093/cid/cit196

Cite this

Rotger, M., Glass, TR., Junier, T., Lundgren, J., Neaton, JD., Poloni, ES., van 't Wout, AB., Lubomirov, R., Colombo, S., Martinez, R., Rauch, A., Gunthard, HF., Neuhaus, J., Wentworth, D., van Manen, D., Gras, LA., Schuitemaker, H., Albini, L., Torti, C., ... 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, 57(1), 112-121. 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 = 2.9x10(-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 exposur 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.",

author = "M Rotger and TR Glass and T Junier and J Lundgren and JD Neaton and ES Poloni and {van 't Wout}, AB and R Lubomirov and S Colombo and R Martinez and Andri Rauch and HF Gunthard and J Neuhaus and D Wentworth and {van Manen}, D and LA Gras and H Schuitemaker and L Albini and C Torti and LP Jacobson and XH Li and LA Kingsley and F Carli and G Guaraldi and ES Ford and I Sereti and C Hadigan and E Martinez and M Arnedo and L Egana-Gorrono and JM Gatell and M Law and C Bendall and K Petoumenos and J Rockstroh and JC Wasmuth and K Kabamba and M Delforge and {de Wit}, S and F Berger and S Mauss and MD Sierra and M Losso and WH Belloso and M Leyes and A Campins and A Mondi and A Luca and I Bernardino and M Barriuso-Iglesias and A Torrecilla-Rodriguez and J Gonzalez-Garcia and JR Arribas and I Fanti and S Gel and J Puig and E Negredo and M Gutierrez and P Domingo and J Fischer and G Fatkenheuer and C Alonso-Villaverde and A Macken and J Woo and T McGinty and P Mallon and A Mangili and S Skinner and CA Wanke and P Reiss and R Weber and HC Bucher and J Fellay and A Telenti and PE Tarr",

year = "2013",

doi = "10.1093/cid/cit196",

language = "Undefined/Unknown",

volume = "57",

pages = "112--121",

journal = "Clinical Infectious Diseases",

issn = "1058-4838",

publisher = "Oxford University Press",

number = "1",

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Rotger, M, Glass, TR, Junier, T, Lundgren, J, Neaton, JD, Poloni, ES, van 't Wout, AB, Lubomirov, R, Colombo, S, Martinez, R, Rauch, A, Gunthard, HF, Neuhaus, J, Wentworth, D, van Manen, D, Gras, LA, Schuitemaker, H, Albini, L, Torti, C, Jacobson, LP, Li, XH, Kingsley, LA, Carli, F, Guaraldi, G, Ford, ES, Sereti, I, Hadigan, C, Martinez, E, Arnedo, M, Egana-Gorrono, L, Gatell, JM, Law, M, Bendall, C, Petoumenos, K, Rockstroh, J, Wasmuth, JC, Kabamba, K, Delforge, M, de Wit, S, Berger, F, Mauss, S, Sierra, MD, Losso, M, Belloso, WH, Leyes, M, Campins, A, Mondi, A, 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, Fatkenheuer, 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, M

AU - Glass, TR

AU - Junier, T

AU - Lundgren, J

AU - Neaton, JD

AU - Poloni, ES

AU - van 't Wout, AB

AU - Lubomirov, R

AU - Colombo, S

AU - Martinez, R

AU - Rauch, Andri

AU - Gunthard, HF

AU - Neuhaus, J

AU - Wentworth, D

AU - van Manen, D

AU - Gras, LA

AU - Schuitemaker, H

AU - Albini, L

AU - Torti, C

AU - Jacobson, LP

AU - Li, XH

AU - Kingsley, LA

AU - Carli, F

AU - Guaraldi, G

AU - Ford, ES

AU - Sereti, I

AU - Hadigan, C

AU - Martinez, E

AU - Arnedo, M

AU - Egana-Gorrono, L

AU - Gatell, JM

AU - Law, M

AU - Bendall, C

AU - Petoumenos, K

AU - Rockstroh, J

AU - Wasmuth, JC

AU - Kabamba, K

AU - Delforge, M

AU - de Wit, S

AU - Berger, F

AU - Mauss, S

AU - Sierra, MD

AU - Losso, M

AU - Belloso, WH

AU - Leyes, M

AU - Campins, A

AU - Mondi, A

AU - Luca, A

AU - Bernardino, I

AU - Barriuso-Iglesias, M

AU - Torrecilla-Rodriguez, A

AU - Gonzalez-Garcia, J

AU - Arribas, JR

AU - Fanti, I

AU - Gel, S

AU - Puig, J

AU - Negredo, E

AU - Gutierrez, M

AU - Domingo, P

AU - Fischer, J

AU - Fatkenheuer, G

AU - Alonso-Villaverde, C

AU - Macken, A

AU - Woo, J

AU - McGinty, T

AU - Mallon, P

AU - Mangili, A

AU - Skinner, S

AU - Wanke, CA

AU - Reiss, P

AU - Weber, R

AU - Bucher, HC

AU - Fellay, J

AU - Telenti, A

AU - Tarr, PE

PY - 2013

Y1 - 2013

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 = 2.9x10(-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 exposur 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 = 2.9x10(-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 exposur 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.

U2 - 10.1093/cid/cit196

DO - 10.1093/cid/cit196

M3 - Article

VL - 57

SP - 112

EP - 121

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

SN - 1058-4838

IS - 1

ER -