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Association Studies of Calcium-Sensing Receptor (CaSR) Polymorphisms with Serum Concentrations of Glucose and Phosphate, and Vascular Calcification in Renal Transplant Recipients.

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Babinsky, Valerie N Hannan, Fadil M Youhanna, Sonia C Maréchal, Céline [UCL] Jadoul, Michel [UCL] Devuyst, Olivier [UCL] Thakker, Rajesh V

(eng) BACKGROUND: Cardiovascular disease is the major cause of death in renal transplant recipients (RTRs) and linked to arterial calcification. The calcium-sensing receptor (CaSR), a G-protein coupled receptor, plays a pivotal role in extracellular calcium homeostasis and is expressed in the intimal and medial layers of the arterial wall. We investigated whether common CASR gene variants are predictors for aortic and coronary artery calcification or influence risk factors such as serum calcium, phosphate and glucose concentrations in RTRs. METHODS: Two hundred and eighty four RTRs were investigated for associations between three CASR promoter region single nucleotide polymorphisms (SNPs) (rs115759455, rs7652589, rs1501899), three non-synonymous CASR coding region SNPs (A986S, R990G, Q1011E), and aortic and coronary artery calcium mass scores, cardiovascular outcomes and calcification risk factors that included serum phosphate, calcium, total cholesterol and glucose concentrations. RESULTS: Multivariate analysis revealed that RTRs homozygous for the minor allele (SS) of the A986S SNP, when compared to those homozygous for the major allele (AA), had raised serum glucose concentrations (8.7±5.4 vs. 5.7±2.1 mmol/L, P<0.05). In addition, RTRs who were heterozygous (CT) at the rs115759455 SNP, when compared to those homozygous for the major allele (CC), had higher serum phosphate concentrations (1.1±0.3 vs. 1.0±0.2 mmol/L, P<0.05). CASR SNPs were not significant determinants for aortic or coronary artery calcification, and were not associated with cardiovascular outcomes or mortality in this RTR cohort. CONCLUSIONS: Common CASR SNPs may be independent predictors of serum glucose and phosphate concentrations, but are not determinants of vascular calcification or cardiovascular outcomes.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès libre
Publication date 2015
Language Anglais
Journal information "PLoS One" - Vol. 10, no. 3, p. e0119459 [1-14] (2015)
Peer reviewed yes
Publisher Public Library of Science ((United States) San Francisco, CA)
e-issn 1932-6203
Publication status Publié
Affiliations UCL - SSS/IREC/NEFR - Pôle de Néphrologie
UCL - (SLuc) Service de néphrologie
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  26. McVean Gil A., Altshuler (Co-Chair) David M., Durbin (Co-Chair) Richard M., Abecasis Gonçalo R., Bentley David R., Chakravarti Aravinda, Clark Andrew G., Donnelly Peter, Eichler Evan E., Flicek Paul, Gabriel Stacey B., Gibbs Richard A., Green Eric D., Hurles Matthew E., Knoppers Bartha M., Korbel Jan O., Lander Eric S., Lee Charles, Lehrach Hans, Mardis Elaine R., Marth Gabor T., McVean Gil A., Nickerson Deborah A., Schmidt Jeanette P., Sherry Stephen T., Wang Jun, Wilson Richard K., Gibbs (Principal Investigator) Richard A., Dinh Huyen, Kovar Christie, Lee Sandra, Lewis Lora, Muzny Donna, Reid Jeff, Wang Min, Wang (Principal Investigator) Jun, Fang Xiaodong, Guo Xiaosen, Jian Min, Jiang Hui, Jin Xin, Li Guoqing, Li Jingxiang, Li Yingrui, Li Zhuo, Liu Xiao, Lu Yao, Ma Xuedi, Su Zhe, Tai Shuaishuai, Tang Meifang, Wang Bo, Wang Guangbiao, Wu Honglong, Wu Renhua, Yin Ye, Zhang Wenwei, Zhao Jiao, Zhao Meiru, Zheng Xiaole, Zhou Yan, Lander (Principal Investigator) Eric S., Altshuler David M., Gabriel (Co-Chair) Stacey B., Gupta Namrata, Flicek (Principal Investigator) Paul, Clarke Laura, Leinonen Rasko, Smith Richard E., Zheng-Bradley Xiangqun, Bentley (Principal Investigator) David R., Grocock Russell, Humphray Sean, James Terena, Kingsbury Zoya, Lehrach (Principal Investigator) Hans, Sudbrak (Project Leader) Ralf, Albrecht Marcus W., Amstislavskiy Vyacheslav S., Borodina Tatiana A., Lienhard Matthias, Mertes Florian, Sultan Marc, Timmermann Bernd, Yaspo Marie-Laure, Sherry (Principal Investigator) Stephen T., McVean (Principal Investigator) Gil A., Mardis (Co-Principal Investigator) (Co-Chair) Elaine R., Wilson (Co-Principal Investigator) Richard K., Fulton Lucinda, Fulton Robert, Weinstock George M., Durbin (Principal Investigator) Richard M., Balasubramaniam Senduran, Burton John, Danecek Petr, Keane Thomas M., Kolb-Kokocinski Anja, McCarthy Shane, Stalker James, Quail Michael, Schmidt (Principal Investigator) Jeanette P., Davies Christopher J., Gollub Jeremy, Webster Teresa, Wong Brant, Zhan Yiping, Auton (Principal Investigator) Adam, Gibbs (Principal Investigator) Richard A., Yu (Project Leader) Fuli, Bainbridge Matthew, Challis Danny, Evani Uday S., Lu James, Muzny Donna, Nagaswamy Uma, Reid Jeff, Sabo Aniko, Wang Yi, Yu Jin, Wang (Principal Investigator) Jun, Coin Lachlan J. M., Fang Lin, Guo Xiaosen, Jin Xin, Li Guoqing, Li Qibin, Li Yingrui, Li Zhenyu, Lin Haoxiang, Liu Binghang, Luo Ruibang, Qin Nan, Shao Haojing, Wang Bingqiang, Xie Yinlong, Ye Chen, Yu Chang, Zhang Fan, Zheng Hancheng, Zhu Hongmei, Marth (Principal Investigator) Gabor T., Garrison Erik P., Kural Deniz, Lee Wan-Ping, Fung Leong Wen, Ward Alistair N., Wu Jiantao, Zhang Mengyao, Lee (Principal Investigator) Charles, Griffin Lauren, Hsieh Chih-Heng, Mills Ryan E., Shi Xinghua, von Grotthuss Marcin, Zhang Chengsheng, Daly (Principal Investigator) Mark J., DePristo (Project Leader) Mark A., Altshuler David M., Banks Eric, Bhatia Gaurav, Carneiro Mauricio O., del Angel Guillermo, Gabriel Stacey B., Genovese Giulio, Gupta Namrata, Handsaker Robert E., Hartl Chris, Lander Eric S., McCarroll Steven A., Nemesh James C., Poplin Ryan E., Schaffner Stephen F., Shakir Khalid, Yoon (Principal Investigator) Seungtai C., Lihm Jayon, Makarov Vladimir, Jin (Principal Investigator) Hanjun, Kim Wook, Cheol Kim Ki, Korbel (Principal Investigator) Jan O., Rausch Tobias, Flicek (Principal Investigator) Paul, Beal Kathryn, Clarke Laura, Cunningham Fiona, Herrero Javier, McLaren William M., Ritchie Graham R. S., Smith Richard E., Zheng-Bradley Xiangqun, Clark (Principal Investigator) Andrew G., Gottipati Srikanth, Keinan Alon, Rodriguez-Flores Juan L., Sabeti (Principal Investigator) Pardis C., Grossman Sharon R., Tabrizi Shervin, Tariyal Ridhi, Cooper (Principal Investigator) David N., Ball Edward V., Stenson Peter D., Bentley (Principal Investigator) David R., Barnes Bret, Bauer Markus, Keira Cheetham R., Cox Tony, Eberle Michael, Humphray Sean, Kahn Scott, Murray Lisa, Peden John, Shaw Richard, Ye (Principal Investigator) Kai, Batzer (Principal Investigator) Mark A., Konkel Miriam K., Walker Jerilyn A., MacArthur (Principal Investigator) Daniel G., Lek Monkol, Sudbrak (Project Leader), Amstislavskiy Vyacheslav S., Herwig Ralf, Shriver (Principal Investigator) Mark D., Bustamante (Principal Investigator) Carlos D., Byrnes Jake K., De La Vega Francisco M., Gravel Simon, Kenny Eimear E., Kidd Jeffrey M., Lacroute Phil, Maples Brian K., Moreno-Estrada Andres, Zakharia Fouad, Halperin (Principal Investigator) Eran, Baran Yael, Craig (Principal Investigator) David W., Christoforides Alexis, Homer Nils, Izatt Tyler, Kurdoglu Ahmet A., Sinari Shripad A., Squire Kevin, Sherry (Principal Investigator) Stephen T., Xiao Chunlin, Sebat (Principal Investigator) Jonathan, Bafna Vineet, Ye Kenny, Burchard (Principal Investigator) Esteban G., Hernandez (Principal Investigator) Ryan D., Gignoux Christopher R., Haussler (Principal Investigator) David, Katzman Sol J., James Kent W., Howie Bryan, Ruiz-Linares (Principal Investigator) Andres, Dermitzakis (Principal Investigator) Emmanouil T., Lappalainen Tuuli, Devine (Principal Investigator) Scott E., Liu Xinyue, Maroo Ankit, Tallon Luke J., Rosenfeld (Principal Investigator) Jeffrey A., Michelson Leslie P., Abecasis (Principal Investigator) (Co-Chair) Gonçalo R., Min Kang (Project Leader) Hyun, Anderson Paul, Angius Andrea, Bigham Abigail, Blackwell Tom, Busonero Fabio, Cucca Francesco, Fuchsberger Christian, Jones Chris, Jun Goo, Li Yun, Lyons Robert, Maschio Andrea, Porcu Eleonora, Reinier Fred, Sanna Serena, Schlessinger David, Sidore Carlo, Tan Adrian, Kate Trost Mary, Awadalla (Principal Investigator) Philip, Hodgkinson Alan, Lunter (Principal Investigator) Gerton, McVean (Principal Investigator) (Co-Chair) Gil A., Marchini (Principal Investigator) Jonathan L., Myers (Principal Investigator) Simon, Churchhouse Claire, Delaneau Olivier, Gupta-Hinch Anjali, Iqbal Zamin, Mathieson Iain, Rimmer Andy, Xifara Dionysia K., Oleksyk (Principal Investigator) Taras K., Fu (Principal Investigator) Yunxin, Liu Xiaoming, Xiong Momiao, Jorde (Principal Investigator) Lynn, Witherspoon David, Xing Jinchuan, Eichler (Principal Investigator) Evan E., Browning (Principal Investigator) Brian L., Alkan Can, Hajirasouliha Iman, Hormozdiari Fereydoun, Ko Arthur, Sudmant Peter H., Mardis (Co-Principal Investigator) Elaine R., Chen Ken, Chinwalla Asif, Ding Li, Dooling David, Koboldt Daniel C., McLellan Michael D., Wallis John W., Wendl Michael C., Zhang Qunyuan, Durbin (Principal Investigator) Richard M., Hurles (Principal Investigator) Matthew E., Albers Cornelis A., Ayub Qasim, Balasubramaniam Senduran, Chen Yuan, Coffey Alison J., Colonna Vincenza, Danecek Petr, Huang Ni, Jostins Luke, Keane Thomas M., Li Heng, McCarthy Shane, Scally Aylwyn, Stalker James, Walter Klaudia, Xue Yali, Zhang Yujun, Gerstein (Principal Investigator) Mark B., Abyzov Alexej, Balasubramanian Suganthi, Chen Jieming, Clarke Declan, Fu Yao, Habegger Lukas, Harmanci Arif O., Jin Mike, Khurana Ekta, Jasmine Mu Xinmeng, Sisu Cristina, Li Yingrui, Luo Ruibang, Zhu Hongmei, Lee (Principal Investigator) (Co-Chair) Charles, Griffin Lauren, Hsieh Chih-Heng, Mills Ryan E., Shi Xinghua, von Grotthuss Marcin, Zhang Chengsheng, Marth (Principal Investigator) Gabor T., Garrison Erik P., Kural Deniz, Lee Wan-Ping, Ward Alistair N., Wu Jiantao, Zhang Mengyao, McCarroll (Project Leader) Steven A., Altshuler David M., Banks Eric, del Angel Guillermo, Genovese Giulio, Handsaker Robert E., Hartl Chris, Nemesh James C., Shakir Khalid, Yoon (Principal Investigator) Seungtai C., Lihm Jayon, Makarov Vladimir, Degenhardt Jeremiah, Flicek (Principal Investigator) Paul, Clarke Laura, Smith Richard E., Zheng-Bradley Xiangqun, Korbel (Principal Investigator) (Co-Chair) Jan O., Rausch Tobias, Stütz Adrian M., Bentley (Principal Investigator) David R., Barnes Bret, Keira Cheetham R., Eberle Michael, Humphray Sean, Kahn Scott, Murray Lisa, Shaw Richard, Ye (Principal Investigator) Kai, Batzer (Principal Investigator) Mark A., Konkel Miriam K., Walker Jerilyn A., Lacroute Phil, Craig (Principal Investigator) David W., Homer Nils, Church Deanna, Xiao Chunlin, Sebat (Principal Investigator) Jonathan, Bafna Vineet, Michaelson Jacob J., Ye Kenny, Devine (Principal Investigator) Scott E., Liu Xinyue, Maroo Ankit, Tallon Luke J., Lunter (Principal Investigator) Gerton, McVean (Principal Investigator) Gil A., Iqbal Zamin, Witherspoon David, Xing Jinchuan, Eichler (Principal Investigator) (Co-Chair) Evan E., Alkan Can, Hajirasouliha Iman, Hormozdiari Fereydoun, Ko Arthur, Sudmant Peter H., Chen Ken, Chinwalla Asif, Ding Li, McLellan Michael D., Wallis John W., Hurles (Principal Investigator) (Co-Chair) Matthew E., Blackburne Ben, Li Heng, Lindsay Sarah J., Ning Zemin, Scally Aylwyn, Walter Klaudia, Zhang Yujun, Gerstein (Principal Investigator) Mark B., Abyzov Alexej, Chen Jieming, Clarke Declan, Khurana Ekta, Jasmine Mu Xinmeng, Sisu Cristina, Gibbs (Principal Investigator) (Co-Chair) Richard A., Yu (Project Leader) Fuli, Bainbridge Matthew, Challis Danny, Evani Uday S., Kovar Christie, Lewis Lora, Lu James, Muzny Donna, Nagaswamy Uma, Reid Jeff, Sabo Aniko, Yu Jin, Guo Xiaosen, Li Yingrui, Wu Renhua, Marth (Principal Investigator) (Co-Chair) Gabor T., Garrison Erik P., Fung Leong Wen, Ward Alistair N., del Angel Guillermo, DePristo Mark A., Gabriel Stacey B., Gupta Namrata, Hartl Chris, Poplin Ryan E., Clark (Principal Investigator) Andrew G., Rodriguez-Flores Juan L., Flicek (Principal Investigator) Paul, Clarke Laura, Smith Richard E., Zheng-Bradley Xiangqun, MacArthur (Principal Investigator) Daniel G., Bustamante (Principal Investigator) Carlos D., Gravel Simon, Craig (Principal Investigator) David W., Christoforides Alexis, Homer Nils, Izatt Tyler, Sherry (Principal Investigator) Stephen T., Xiao Chunlin, Dermitzakis (Principal Investigator) Emmanouil T., Abecasis (Principal Investigator) Gonçalo R., Min Kang Hyun, McVean (Principal Investigator) Gil A., Mardis (Principal Investigator) Elaine R., Dooling David, Fulton Lucinda, Fulton Robert, Koboldt Daniel C., Durbin (Principal Investigator) Richard M., Balasubramaniam Senduran, Keane Thomas M., McCarthy Shane, Stalker James, Gerstein (Principal Investigator) Mark B., Balasubramanian Suganthi, Habegger Lukas, Garrison Erik P., Gibbs (Principal Investigator) Richard A., Bainbridge Matthew, Muzny Donna, Yu Fuli, Yu Jin, del Angel Guillermo, Handsaker Robert E., Makarov Vladimir, Rodriguez-Flores Juan L., Jin (Principal Investigator) Hanjun, Kim Wook, Cheol Kim Ki, Flicek (Principal Investigator) Paul, Beal Kathryn, Clarke Laura, Cunningham Fiona, Herrero Javier, McLaren William M., Ritchie Graham R. S., Zheng-Bradley Xiangqun, Tabrizi Shervin, MacArthur (Principal Investigator) Daniel G., Lek Monkol, Bustamante (Principal Investigator) Carlos D., De La Vega Francisco M., Craig (Principal Investigator) David W., Kurdoglu Ahmet A., Lappalainen Tuuli, Rosenfeld (Principal Investigator) Jeffrey A., Michelson Leslie P., Awadalla (Principal Investigator) Philip, Hodgkinson Alan, McVean (Principal Investigator) Gil A., Chen Ken, Chen Yuan, Colonna Vincenza, Frankish Adam, Harrow Jennifer, Xue Yali, Gerstein (Principal Investigator) (Co-Chair) Mark B., Abyzov Alexej, Balasubramanian Suganthi, Chen Jieming, Clarke Declan, Fu Yao, Harmanci Arif O., Jin Mike, Khurana Ekta, Jasmine Mu Xinmeng, Sisu Cristina, Gibbs (Principal Investigator) Richard A., Fowler Gerald, Hale Walker, Kalra Divya, Kovar Christie, Muzny Donna, Reid Jeff, Wang (Principal Investigator) Jun, Guo Xiaosen, Li Guoqing, Li Yingrui, Zheng Xiaole, Altshuler David M., Flicek (Principal Investigator) (Co-Chair) Paul, Clarke (Project Leader) Laura, Barker Jonathan, Kelman Gavin, Kulesha Eugene, Leinonen Rasko, McLaren William M., Radhakrishnan Rajesh, Roa Asier, Smirnov Dmitriy, Smith Richard E., Streeter Ian, Toneva Iliana, Vaughan Brendan, Zheng-Bradley Xiangqun, Bentley (Principal Investigator) David R., Cox Tony, Humphray Sean, Kahn Scott, Sudbrak (Project Leader) Ralf, Albrecht Marcus W., Lienhard Matthias, Craig (Principal Investigator) David W., Izatt Tyler, Kurdoglu Ahmet A., Sherry (Principal Investigator) (Co-Chair) Stephen T., Ananiev Victor, Belaia Zinaida, Beloslyudtsev Dimitriy, Bouk Nathan, Chen Chao, Church Deanna, Cohen Robert, Cook Charles, Garner John, Hefferon Timothy, Kimelman Mikhail, Liu Chunlei, Lopez John, Meric Peter, O’Sullivan Chris, Ostapchuk Yuri, Phan Lon, Ponomarov Sergiy, Schneider Valerie, Shekhtman Eugene, Sirotkin Karl, Slotta Douglas, Xiao Chunlin, Zhang Hua, Haussler (Principal Investigator) David, Abecasis (Principal Investigator) Gonçalo R., McVean (Principal Investigator) Gil A., Alkan Can, Ko Arthur, Dooling David, Durbin (Principal Investigator) Richard M., Balasubramaniam Senduran, Keane Thomas M., McCarthy Shane, Stalker James, Chakravarti (Co-Chair) Aravinda, Knoppers (Co-Chair) Bartha M., Abecasis Gonçalo R., Barnes Kathleen C., Beiswanger Christine, Burchard Esteban G., Bustamante Carlos D., Cai Hongyu, Cao Hongzhi, Durbin Richard M., Gharani Neda, Gibbs Richard A., Gignoux Christopher R., Gravel Simon, Henn Brenna, Jones Danielle, Jorde Lynn, Kaye Jane S., Keinan Alon, Kent Alastair, Kerasidou Angeliki, Li Yingrui, Mathias Rasika, McVean Gil A., Moreno-Estrada Andres, Ossorio Pilar N., Parker Michael, Reich David, Rotimi Charles N., Royal Charmaine D., Sandoval Karla, Su Yeyang, Sudbrak Ralf, Tian Zhongming, Timmermann Bernd, Tishkoff Sarah, Toji Lorraine H., Tyler Smith Chris, Via Marc, Wang Yuhong, Yang Huanming, Yang Ling, Zhu Jiayong, Bodmer Walter, Bedoya Gabriel, Ruiz-Linares Andres, Zhi Ming Cai, Yang Gao, Jia You Chu, Peltonen Leena, Garcia-Montero Andres, Orfao Alberto, Dutil Julie, Martinez-Cruzado Juan C., Oleksyk Taras K., Brooks Lisa D., Felsenfeld Adam L., McEwen Jean E., Clemm Nicholas C., Duncanson Audrey, Dunn Michael, Green Eric D., Guyer Mark S., Peterson Jane L., Abecasis Goncalo R., Auton Adam, Brooks Lisa D., DePristo Mark A., Durbin Richard M., Handsaker Robert E., Min Kang Hyun, Marth Gabor T., McVean Gil A., An integrated map of genetic variation from 1,092 human genomes, 10.1038/nature11632
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Bibliographic reference Babinsky, Valerie N ; Hannan, Fadil M ; Youhanna, Sonia C ; Maréchal, Céline ; Jadoul, Michel ; et. al. Association Studies of Calcium-Sensing Receptor (CaSR) Polymorphisms with Serum Concentrations of Glucose and Phosphate, and Vascular Calcification in Renal Transplant Recipients.. In: PLoS One, Vol. 10, no. 3, p. e0119459 [1-14] (2015)
Permanent URL http://hdl.handle.net/2078.1/158552