Association of Candidate Gene Polymorphisms With Chronic Kidney Disease: Results of a Case-Control Analysis in the Nefrona Cohort
Por:
Valls, J, Cambray, S, Perez-Guallar, C, Bozic, M, Bermudez-Lopez, M, Fernandez, E, Betriu, A, Rodriguez, I, Valdivielso, JM, Regidor, MJA, Almirall, J, Ponz, E, Coloma, JA, Rubio, MAB, Diaz, RR, Rodriguez, MB, Gascon, A, Sanjuan, JB, Artero, JB, Romero, JBC, Cases, SM, Varela, JC, Acevedo, PC, Bassa, JC, Amenos, AC, Jimenez, EM, Lopez, RM, Guldris, SC, Prieto, SL, Mongay, LC, Comerma, I, Jove, MTC, Izquierdo, MC, de Alvaro, F, Ojanguren, CH, de la Fuente, GD, Pino, MDDY, Izquierdo, RDT, Hormigos, FA, Dotori, M, Duarte, V, Torres, SE, Reyes, MJF, Rodriguez, MLF, Fernandez, G, Serrano, AG, Canton, CG, Herrera, ALG, Mena, MG, Sacaluga, LG, Aguilar, M, Gorriz, JL, Loza, EH, Lerma, JL, Canada, AL, Alvarez, JPM, Alemany, NM, Garcia, JM, Castelao, AM, Villaescusa, MM, Martinez, I, Eguren, IM, Los Huertos, SM, Mirco, RM, Vila, AM, Diaz, ABM, Gonzalez, JFN, Nieto, J, Carreno, A, Fernandez, EN, Ortiz, A, Fernandez, B, Paraiso, V, Fontan, MP, Domingo, AP, Haces, CP, Garrido, MDP, Velasco, MP, Mari, CP, Gorrin, MR, Rubio, E, Ruiz, P, Lazo, MS, Puerto, AIM, Tomero, JAS, Sanchez, JE, Lorman, RS, Saracho, R, Sarrias, M, Seron, D, Soler, MJ, Barrios, C, Sousa, F, Toran, D, Molina, FT, Carrasco, JJU, Cortes, IV, del Perugia, MMV, Ruiz, RCV, Altozano, CS, Rodenas, MA, Gil, IG, Gil, FA, Criado, EG, Belinchon, RD, Toro, JMF, Garrote, JAD
Publicada:
26 feb 2019
Resumen:
Chronic kidney disease (CKD) is a major risk factor for end-stage renal disease, cardiovascular disease and premature death. Despite classical clinical risk factors for CKD and some genetic risk factors have been identified, the residual risk observed in prediction models is still high. Therefore, new risk factors need to be identified in order to better predict the risk of CKD in the population. Here, we analyzed the genetic association of 79 SNPs of proteins associated with mineral metabolism disturbances with CKD in a cohort that includes 2,445 CKD cases and 559 controls. Genotyping was performed with matrix assisted laser desorption ionizationtime of flight mass spectrometry. We used logistic regression models considering different genetic inheritance models to assess the association of the SNPs with the prevalence of CKD, adjusting for known risk factors. Eight SNPs (rs1126616, rs35068180, rs2238135, rs1800247, rs385564, rs4236, rs2248359, and rs1564858) were associated with CKD even after adjusting by sex, age and race. A model containing five of these SNPs (rs1126616, rs35068180, rs1800247, rs4236, and rs2248359), diabetes and hypertension showed better performance than models considering only clinical risk factors, significantly increasing the area under the curve of the model without polymorphisms. Furthermore, one of the SNPs (the rs2248359) showed an interaction with hypertension, being the risk genotype affecting only hypertensive patients. We conclude that 5 SNPs related to proteins implicated in mineral metabolism disturbances (Osteopontin, osteocalcin, matrix gla protein, matrix metalloprotease 3 and 24 hydroxylase) are associated to an increased risk of suffering CKD.
Filiaciones:
Valls, J:
Inst Salud Carlos 3, Inst Recerca Brorned Lleida & Redes, Biostat Unit, Lleida, Spain
Cambray, S:
Inst Recerca Biomed Lleida, Biomed Res Inst, Vasc & Renal Transiatkoal Res Grp, Lleida, Spain
Perez-Guallar, C:
Inst Salud Carlos 3, Inst Recerca Brorned Lleida & Redes, Biostat Unit, Lleida, Spain
Bozic, M:
Inst Recerca Biomed Lleida, Biomed Res Inst, Vasc & Renal Transiatkoal Res Grp, Lleida, Spain
Bermudez-Lopez, M:
Inst Recerca Biomed Lleida, Biomed Res Inst, Vasc & Renal Transiatkoal Res Grp, Lleida, Spain
Fernandez, E:
Inst Recerca Biomed Lleida, Biomed Res Inst, Vasc & Renal Transiatkoal Res Grp, Lleida, Spain
Complexo Hosp Ourense, Orense, Spain
Betriu, A:
Inst Recerca Biomed Lleida, Biomed Res Inst, Vasc & Renal Transiatkoal Res Grp, Lleida, Spain
Rodriguez, I:
RedinRen ISCIII, Lleida, Spain
Univ Oviedo, Inst Invest Santana Principado Asturias, Hosp Univ Cent Asturias, Bone & Mineral Res Unit,RedinRen ISCIII, Oviedo, Spain
Valdivielso, JM:
Inst Recerca Biomed Lleida, Biomed Res Inst, Vasc & Renal Transiatkoal Res Grp, Lleida, Spain
Regidor, MJA:
Hosp Comarcal Ernest Lluch, Calatayud, Spain
Almirall, J:
Corporacid Parc Tauli, Barcelona, Spain
Ponz, E:
Corporacid Parc Tauli, Barcelona, Spain
Coloma, JA:
Hosp Navarra, Pamplona, Spain
Rubio, MAB:
Auxiliadora, Pamplona, Spain
Diaz, RR:
Hosp La Paz, Madrid, Spain
Rodriguez, MB:
Montserrat Sistemes Renals, Lleida, Spain
Gascon, A:
Hosp Obispo Polanco, Teruel, Spain
Sanjuan, JB:
IIB St Pau, Fundacio Puigvert, Barcelona, Spain
Artero, JB:
Clin Girona, Girona, Spain
Romero, JBC:
Hosp Reina Sofia, Murcia, Spain
Cases, SM:
Hosp Reina Sofia, Murcia, Spain
Varela, JC:
Hosp Univ Lucus Augusti, Lugo, Spain
Acevedo, PC:
Clin Ruber, Madrid, Spain
Bassa, JC:
Diaverum Baix Llobregat, Barcelona, Spain
Amenos, AC:
Hosp Clin Barcelona, Barcelona, Spain
Jimenez, EM:
Hosp Clin Barcelona, Barcelona, Spain
Lopez, RM:
Hosp Defensa, Zaragoza, Spain
Guldris, SC:
Hosp Costa, Lugo, Spain
Prieto, SL:
Hosp Costa, Lugo, Spain
Mongay, LC:
Lourdes Hosp Gen Vic, Barcelona, Spain
Comerma, I:
Hosp Gen Manresa, Barcelona, Spain
Jove, MTC:
Hosp Santa Creu Jesus, Tarragona, Spain
Izquierdo, MC:
Hosp Reina Sofia, Navarra, Spain
de Alvaro, F:
Hosp Infanta Sofia, Madrid, Spain
Ojanguren, CH:
Hosp Infanta Sofia, Madrid, Spain
de la Fuente, GD:
Hosp Univ Guadalajara, Guadalajara, Spain
Pino, MDDY:
Complejo Hosp Torrecardenas Almeria, Almeria, Spain
Izquierdo, RDT:
Hosp Virgen Salud, Toledo, Spain
Hormigos, FA:
Hosp Virgen Salud, Toledo, Spain
Dotori, M:
USP Marbella, Marbella, Spain
Duarte, V:
Hosp Terrassa, Barcelona, Spain
Torres, SE:
Hosp Univ Canarias, Santa Cruz De Tenerife, Spain
Reyes, MJF:
Hosp Segovia, Segovia, Spain
Rodriguez, MLF:
Hosp Principe Asturias, Madrid, Spain
Fernandez, G:
Clin Santa Isabel, Seville, Spain
Serrano, AG:
Hosp Gen Univ Valencia, Valencia, Spain
Canton, CG:
Hosp Univ Insular Gran Canaria, Las Palmas Gran Canaria, Spain
Herrera, ALG:
Hosp Univ Puerto Real, Cadiz, Spain
Mena, MG:
Hosp San Juan Dios, Zaragoza, Spain
Sacaluga, LG:
Hosp Virgen Rocio, Seville, Spain
Aguilar, M:
Hosp Virgen Rocio, Seville, Spain
Gorriz, JL:
Hosp Univ Doctor Peset, Valencia, Spain
Loza, EH:
Hosp San Pedro, Logrono, Spain
Lerma, JL:
Hosp San Pedro Alcantara, Caceres, Spain
Canada, AL:
Hosp San Pedro Alcantara, Caceres, Spain
Alvarez, JPM:
Hosp San Pedro Alcantara, Caceres, Spain
Alemany, NM:
Hosp Univ Dr Josep Trueta, Girona, Spain
Garcia, JM:
Hosp Nuestra Senora Sonsoles, Avila, Spain
Castelao, AM:
Hosp Univ Bellvitge, Barcelona, Spain
Villaescusa, MM:
Hosp Univ Albacete, Albacete, Spain
Martinez, I:
Hosp Galdakao, Bilbao, Spain
Eguren, IM:
Inigo Hosp Basurto, Bilbao, Spain
Los Huertos, SM:
Hosp Santa Barbara, Soria, Spain
Mirco, RM:
Hosp Bierzo Ponferrada, Leon, Spain
Vila, AM:
Hosp Univ Son Espases, Palma De Mallorca, Spain
Diaz, ABM:
Hosp Vithas Nisa Virgen Consuelo, Valencia, Spain
Gonzalez, JFN:
Hosp Univ Nuestra Senora Candelaria, Santa Cruz De Tenerife, Spain
Nieto, J:
Hosp Gen Univ Ciudad Real, Ciudad Real, Spain
Carreno, A:
Hosp Gen Univ Ciudad Real, Ciudad Real, Spain
Fernandez, EN:
Complexo Hosp Ourense, Orense, Spain
Ortiz, A:
IIS Fundac Jimenez Diaz, Madrid, Spain
Fernandez, B:
IIS Fundac Jimenez Diaz, Madrid, Spain
Paraiso, V:
Hosp Univ Henares, Madrid, Spain
Fontan, MP:
Complejo Hosp Univ A Coruna, La Coruna, Spain
Domingo, AP:
Hosp Francesc Borja, Valencia, Spain
Haces, CP:
Hosp Univ Marques Valdecilla, Santander, Spain
Garrido, MDP:
Hosp Univ San Cecilio, Granada, Spain
Velasco, MP:
Mario Hosp Leon, Leon, Spain
Mari, CP:
Hosp Igualada, Barcelona, Spain
Gorrin, MR:
Hosp Univ Ramon & Cajal, Madrid, Spain
Rubio, E:
Hosp Puerta Hierro Majadahonda, Madrid, Spain
Ruiz, P:
Hosp St Joan Despi Moises Broggi, Barcelona, Spain
Lazo, MS:
Hosp Univ Virgen Macarena, Seville, Spain
Puerto, AIM:
Hosp Univ Virgen Macarena, Seville, Spain
Tomero, JAS:
Hosp Univ Princesa, Madrid, Spain
Sanchez, JE:
Hosp Univ Cent Asturias, Oviedo, Spain
Lorman, RS:
Hosp Figueres, Girona, Spain
Saracho, R:
Hosp Santiago, Vitoria, Spain
Sarrias, M:
Hosp Univ Vali Hebron, Barcelona, Spain
Seron, D:
Hosp Univ Vali Hebron, Barcelona, Spain
Soler, MJ:
Hosp Mar, Barcelona, Spain
Barrios, C:
Hosp Mar, Barcelona, Spain
Sousa, F:
Hosp Rio Carrion, Palencia, Spain
Toran, D:
Hosp Gen Jerez, Cadiz, Spain
Molina, FT:
Hosp Univ Del Sureste, Arganda Del Rey, Spain
Carrasco, JJU:
Hosp Virgen Luz, Cuenca, Spain
Cortes, IV:
Hosp Virgen Victoria, Cuenca, Spain
del Perugia, MMV:
Inst Catala Urol & Nefrol, Barcelona, Spain
Ruiz, RCV:
Hosp San Jorge, Huesca, Spain
Altozano, CS:
Azuqueca Henares, Guadalajara, Spain
Rodenas, MA:
CS Zona III, Albacete, Spain
Gil, IG:
CAP Viella, Lleida, Spain
Gil, FA:
Francisco Adan Gil CS Alfaro, La Rioja, Spain
Criado, EG:
Criado Ctr Salud Carpio, Cordoba, Spain
Belinchon, RD:
Belinchon CS Godella, Valencia, Spain
Toro, JMF:
CS Zona Ctr, Caceres, Spain
Garrote, JAD:
Garrote Ctr Salud Casas Ibanez, Albacete, Spain
Gold, Green Published
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