Genetic contributors to serum uric acid levels in Mexicans and their effect on premature coronary artery disease

Luis R. Macias-Kauffer, Hugo Villamil-Ramírez, Paola León-Mimila, Leonor Jacobo-Albavera, Carlos Posadas-Romero, Rosalinda Posadas-Sánchez, Blanca E. López-Contreras, Sofía Morán-Ramos, Sandra Romero-Hidalgo, Víctor Acuña-Alonzo, Blanca E. del-Río-Navarro, Maria Cátira Bortolini, Carla Gallo, Gabriel Bedoya, Francisco Rothhammer, Rolando González-Jose, Andrés Ruiz-Linares, Christopher R. Stephens, Rafael Velazquez-Cruz, Cecilia Fernández del Valle-LaisequillaJuan G. Reyes-García, Lina M. Barranco Garduño, Miriam del C. Carrasco-Portugal, Francisco J. Flores-Murrieta, Gilberto Vargas-Alarcón, Carlos A. Aguilar-Salinas, Teresa Villarreal-Molina, Samuel Canizales-Quinteros

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Abstract

© 2018 Elsevier B.V. Background: Serum uric acid (SUA) is a heritable trait associated with cardiovascular risk factors and coronary artery disease (CAD). Genome wide association studies (GWAS) have identified several genes associated with SUA, mainly in European populations. However, to date there are few GWAS in Latino populations, and the role of SUA-associated single nucleotide polymorphisms (SNPs) in cardiovascular disease has not been studied in the Mexican population. Methods: We performed genome-wide SUA association study in 2153 Mexican children and adults, evaluated whether genetic effects were modified by sex and obesity, and used a Mendelian randomization approach in an independent cohort to study the role of SUA modifying genetic variants in premature CAD. Results: Only two loci were associated with SUA levels: SLC2A9 (β = −0.47 mg/dl, P = 1.57 × 10−42 for lead SNP rs7678287) and ABCG2 (β = 0.23 mg/dl, P = 2.42 × 10−10 for lead SNP rs2231142). No significant interaction between SLC2A9 rs7678287 and ABCG2 rs2231142 genotypes and obesity was observed. However, a significant ABCG2 rs2231142 genotype*sex interaction (P = 0.001) was observed in adults but not in children. Although SUA levels were associated with premature CAD, metabolic syndrome and decreased glomerular filtration rate (eGFR), only ABCG2 rs2231142 was associated with decreased eGFR in the premature CAD group. Conclusions: SUA elevation was independently associated with premature CAD, metabolic syndrome and decreased eGFR in the Mexican population. However, a Mendelian randomization approach using the lead SUA-associated SNPs (SLC2A9 and ABCG2) did not support a causal role of elevated SUA levels for premature CAD.
Original languageAmerican English
Pages (from-to)168-173
Number of pages150
JournalInternational Journal of Cardiology
DOIs
StatePublished - 15 Mar 2019

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Uric Acid
Coronary Artery Disease
Serum
Single Nucleotide Polymorphism
Genome-Wide Association Study
Random Allocation
Population
Obesity
Genotype
Glomerular Filtration Rate
Hispanic Americans
Cohort Studies
Cardiovascular Diseases
Genome

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Macias-Kauffer, L. R., Villamil-Ramírez, H., León-Mimila, P., Jacobo-Albavera, L., Posadas-Romero, C., Posadas-Sánchez, R., ... Canizales-Quinteros, S. (2019). Genetic contributors to serum uric acid levels in Mexicans and their effect on premature coronary artery disease. International Journal of Cardiology, 168-173. https://doi.org/10.1016/j.ijcard.2018.09.107
Macias-Kauffer, Luis R. ; Villamil-Ramírez, Hugo ; León-Mimila, Paola ; Jacobo-Albavera, Leonor ; Posadas-Romero, Carlos ; Posadas-Sánchez, Rosalinda ; López-Contreras, Blanca E. ; Morán-Ramos, Sofía ; Romero-Hidalgo, Sandra ; Acuña-Alonzo, Víctor ; del-Río-Navarro, Blanca E. ; Bortolini, Maria Cátira ; Gallo, Carla ; Bedoya, Gabriel ; Rothhammer, Francisco ; González-Jose, Rolando ; Ruiz-Linares, Andrés ; Stephens, Christopher R. ; Velazquez-Cruz, Rafael ; Fernández del Valle-Laisequilla, Cecilia ; Reyes-García, Juan G. ; Barranco Garduño, Lina M. ; Carrasco-Portugal, Miriam del C. ; Flores-Murrieta, Francisco J. ; Vargas-Alarcón, Gilberto ; Aguilar-Salinas, Carlos A. ; Villarreal-Molina, Teresa ; Canizales-Quinteros, Samuel. / Genetic contributors to serum uric acid levels in Mexicans and their effect on premature coronary artery disease. In: International Journal of Cardiology. 2019 ; pp. 168-173.
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title = "Genetic contributors to serum uric acid levels in Mexicans and their effect on premature coronary artery disease",
abstract = "{\circledC} 2018 Elsevier B.V. Background: Serum uric acid (SUA) is a heritable trait associated with cardiovascular risk factors and coronary artery disease (CAD). Genome wide association studies (GWAS) have identified several genes associated with SUA, mainly in European populations. However, to date there are few GWAS in Latino populations, and the role of SUA-associated single nucleotide polymorphisms (SNPs) in cardiovascular disease has not been studied in the Mexican population. Methods: We performed genome-wide SUA association study in 2153 Mexican children and adults, evaluated whether genetic effects were modified by sex and obesity, and used a Mendelian randomization approach in an independent cohort to study the role of SUA modifying genetic variants in premature CAD. Results: Only two loci were associated with SUA levels: SLC2A9 (β = −0.47 mg/dl, P = 1.57 × 10−42 for lead SNP rs7678287) and ABCG2 (β = 0.23 mg/dl, P = 2.42 × 10−10 for lead SNP rs2231142). No significant interaction between SLC2A9 rs7678287 and ABCG2 rs2231142 genotypes and obesity was observed. However, a significant ABCG2 rs2231142 genotype*sex interaction (P = 0.001) was observed in adults but not in children. Although SUA levels were associated with premature CAD, metabolic syndrome and decreased glomerular filtration rate (eGFR), only ABCG2 rs2231142 was associated with decreased eGFR in the premature CAD group. Conclusions: SUA elevation was independently associated with premature CAD, metabolic syndrome and decreased eGFR in the Mexican population. However, a Mendelian randomization approach using the lead SUA-associated SNPs (SLC2A9 and ABCG2) did not support a causal role of elevated SUA levels for premature CAD.",
author = "Macias-Kauffer, {Luis R.} and Hugo Villamil-Ram{\'i}rez and Paola Le{\'o}n-Mimila and Leonor Jacobo-Albavera and Carlos Posadas-Romero and Rosalinda Posadas-S{\'a}nchez and L{\'o}pez-Contreras, {Blanca E.} and Sof{\'i}a Mor{\'a}n-Ramos and Sandra Romero-Hidalgo and V{\'i}ctor Acu{\~n}a-Alonzo and del-R{\'i}o-Navarro, {Blanca E.} and Bortolini, {Maria C{\'a}tira} and Carla Gallo and Gabriel Bedoya and Francisco Rothhammer and Rolando Gonz{\'a}lez-Jose and Andr{\'e}s Ruiz-Linares and Stephens, {Christopher R.} and Rafael Velazquez-Cruz and {Fern{\'a}ndez del Valle-Laisequilla}, Cecilia and Reyes-Garc{\'i}a, {Juan G.} and {Barranco Gardu{\~n}o}, {Lina M.} and Carrasco-Portugal, {Miriam del C.} and Flores-Murrieta, {Francisco J.} and Gilberto Vargas-Alarc{\'o}n and Aguilar-Salinas, {Carlos A.} and Teresa Villarreal-Molina and Samuel Canizales-Quinteros",
year = "2019",
month = "3",
day = "15",
doi = "10.1016/j.ijcard.2018.09.107",
language = "American English",
pages = "168--173",
journal = "International Journal of Cardiology",
issn = "0167-5273",
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Macias-Kauffer, LR, Villamil-Ramírez, H, León-Mimila, P, Jacobo-Albavera, L, Posadas-Romero, C, Posadas-Sánchez, R, López-Contreras, BE, Morán-Ramos, S, Romero-Hidalgo, S, Acuña-Alonzo, V, del-Río-Navarro, BE, Bortolini, MC, Gallo, C, Bedoya, G, Rothhammer, F, González-Jose, R, Ruiz-Linares, A, Stephens, CR, Velazquez-Cruz, R, Fernández del Valle-Laisequilla, C, Reyes-García, JG, Barranco Garduño, LM, Carrasco-Portugal, MDC, Flores-Murrieta, FJ, Vargas-Alarcón, G, Aguilar-Salinas, CA, Villarreal-Molina, T & Canizales-Quinteros, S 2019, 'Genetic contributors to serum uric acid levels in Mexicans and their effect on premature coronary artery disease', International Journal of Cardiology, pp. 168-173. https://doi.org/10.1016/j.ijcard.2018.09.107

Genetic contributors to serum uric acid levels in Mexicans and their effect on premature coronary artery disease. / Macias-Kauffer, Luis R.; Villamil-Ramírez, Hugo; León-Mimila, Paola; Jacobo-Albavera, Leonor; Posadas-Romero, Carlos; Posadas-Sánchez, Rosalinda; López-Contreras, Blanca E.; Morán-Ramos, Sofía; Romero-Hidalgo, Sandra; Acuña-Alonzo, Víctor; del-Río-Navarro, Blanca E.; Bortolini, Maria Cátira; Gallo, Carla; Bedoya, Gabriel; Rothhammer, Francisco; González-Jose, Rolando; Ruiz-Linares, Andrés; Stephens, Christopher R.; Velazquez-Cruz, Rafael; Fernández del Valle-Laisequilla, Cecilia; Reyes-García, Juan G.; Barranco Garduño, Lina M.; Carrasco-Portugal, Miriam del C.; Flores-Murrieta, Francisco J.; Vargas-Alarcón, Gilberto; Aguilar-Salinas, Carlos A.; Villarreal-Molina, Teresa; Canizales-Quinteros, Samuel.

In: International Journal of Cardiology, 15.03.2019, p. 168-173.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Genetic contributors to serum uric acid levels in Mexicans and their effect on premature coronary artery disease

AU - Macias-Kauffer, Luis R.

AU - Villamil-Ramírez, Hugo

AU - León-Mimila, Paola

AU - Jacobo-Albavera, Leonor

AU - Posadas-Romero, Carlos

AU - Posadas-Sánchez, Rosalinda

AU - López-Contreras, Blanca E.

AU - Morán-Ramos, Sofía

AU - Romero-Hidalgo, Sandra

AU - Acuña-Alonzo, Víctor

AU - del-Río-Navarro, Blanca E.

AU - Bortolini, Maria Cátira

AU - Gallo, Carla

AU - Bedoya, Gabriel

AU - Rothhammer, Francisco

AU - González-Jose, Rolando

AU - Ruiz-Linares, Andrés

AU - Stephens, Christopher R.

AU - Velazquez-Cruz, Rafael

AU - Fernández del Valle-Laisequilla, Cecilia

AU - Reyes-García, Juan G.

AU - Barranco Garduño, Lina M.

AU - Carrasco-Portugal, Miriam del C.

AU - Flores-Murrieta, Francisco J.

AU - Vargas-Alarcón, Gilberto

AU - Aguilar-Salinas, Carlos A.

AU - Villarreal-Molina, Teresa

AU - Canizales-Quinteros, Samuel

PY - 2019/3/15

Y1 - 2019/3/15

N2 - © 2018 Elsevier B.V. Background: Serum uric acid (SUA) is a heritable trait associated with cardiovascular risk factors and coronary artery disease (CAD). Genome wide association studies (GWAS) have identified several genes associated with SUA, mainly in European populations. However, to date there are few GWAS in Latino populations, and the role of SUA-associated single nucleotide polymorphisms (SNPs) in cardiovascular disease has not been studied in the Mexican population. Methods: We performed genome-wide SUA association study in 2153 Mexican children and adults, evaluated whether genetic effects were modified by sex and obesity, and used a Mendelian randomization approach in an independent cohort to study the role of SUA modifying genetic variants in premature CAD. Results: Only two loci were associated with SUA levels: SLC2A9 (β = −0.47 mg/dl, P = 1.57 × 10−42 for lead SNP rs7678287) and ABCG2 (β = 0.23 mg/dl, P = 2.42 × 10−10 for lead SNP rs2231142). No significant interaction between SLC2A9 rs7678287 and ABCG2 rs2231142 genotypes and obesity was observed. However, a significant ABCG2 rs2231142 genotype*sex interaction (P = 0.001) was observed in adults but not in children. Although SUA levels were associated with premature CAD, metabolic syndrome and decreased glomerular filtration rate (eGFR), only ABCG2 rs2231142 was associated with decreased eGFR in the premature CAD group. Conclusions: SUA elevation was independently associated with premature CAD, metabolic syndrome and decreased eGFR in the Mexican population. However, a Mendelian randomization approach using the lead SUA-associated SNPs (SLC2A9 and ABCG2) did not support a causal role of elevated SUA levels for premature CAD.

AB - © 2018 Elsevier B.V. Background: Serum uric acid (SUA) is a heritable trait associated with cardiovascular risk factors and coronary artery disease (CAD). Genome wide association studies (GWAS) have identified several genes associated with SUA, mainly in European populations. However, to date there are few GWAS in Latino populations, and the role of SUA-associated single nucleotide polymorphisms (SNPs) in cardiovascular disease has not been studied in the Mexican population. Methods: We performed genome-wide SUA association study in 2153 Mexican children and adults, evaluated whether genetic effects were modified by sex and obesity, and used a Mendelian randomization approach in an independent cohort to study the role of SUA modifying genetic variants in premature CAD. Results: Only two loci were associated with SUA levels: SLC2A9 (β = −0.47 mg/dl, P = 1.57 × 10−42 for lead SNP rs7678287) and ABCG2 (β = 0.23 mg/dl, P = 2.42 × 10−10 for lead SNP rs2231142). No significant interaction between SLC2A9 rs7678287 and ABCG2 rs2231142 genotypes and obesity was observed. However, a significant ABCG2 rs2231142 genotype*sex interaction (P = 0.001) was observed in adults but not in children. Although SUA levels were associated with premature CAD, metabolic syndrome and decreased glomerular filtration rate (eGFR), only ABCG2 rs2231142 was associated with decreased eGFR in the premature CAD group. Conclusions: SUA elevation was independently associated with premature CAD, metabolic syndrome and decreased eGFR in the Mexican population. However, a Mendelian randomization approach using the lead SUA-associated SNPs (SLC2A9 and ABCG2) did not support a causal role of elevated SUA levels for premature CAD.

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Macias-Kauffer LR, Villamil-Ramírez H, León-Mimila P, Jacobo-Albavera L, Posadas-Romero C, Posadas-Sánchez R et al. Genetic contributors to serum uric acid levels in Mexicans and their effect on premature coronary artery disease. International Journal of Cardiology. 2019 Mar 15;168-173. https://doi.org/10.1016/j.ijcard.2018.09.107