Common variants in the ATP2B1 gene are associated with susceptibility to hypertension: the Japanese Millennium Genome Project

Y Tabara; K Kohara; Y Kita; N Hirawa; T Katsuya; T Ohkubo; Y Hiura; A Tajima; T Morisaki; T Miyata; T Nakayama; N Takashima; J Nakura; R Kawamoto; N Takahashi; A Hata; M Soma; Y Imai; Y Kokubo; T Okamura; H Tomoike; N Iwai; T Ogihara; I Inoue; K Tokunaga; T Johnson; M Caulfield; P Munroe; Global Blood Pressure Genetics Consortium; S Umemura; H Ueshima; T. Collaborators: Newton Cheh C Miki; T Johnson; V Gateva; MD Tobin; M Bochud; L Coin; SS Najjar; JH Zhao; SC Heath; S Eyheramendy; K Papadakis; BF Voight; LJ Scott; F Zhang; M Farrall; T Tanaka; C Wallace; JC Chambers; KT Khaw; P Nilsson; der Harst P van; Silvia POLIDORO; DE Grobbee; Moret NC Onland; ML Bots; LV Wain; KS Elliott; A Teumer; J Luan; G Lucas; J Kuusisto; PR Burton; D Hadley; WL McArdle; M Brown; A Dominiczak; SJ Newhouse; NJ Samani; J Webster; E Zeggini; JS Beckmann; S Bergmann; N Lim; K Song; P Vollenweider; G Waeber; DM Waterworth; X Yuan; L Groop; Melander M Orho; A Allione; ALESSANDRA DI GREGORIO; GUARRERA Simonetta; S Panico; FULVIO RICCERI; VALERIA ROMANAZZI; Carlotta SACERDOTE; VINEIS Paolo; I Barroso; MS Sandhu; RN Luben; GJ Crawford; P Jousilahti; M Perola; M Boehnke; LL Bonnycastle; FS Collins; AU Jackson; KL Mohlke; HM Stringham; TT Valle; CJ Willer; RN Bergman; MA Morken; A Döring; C Gieger; T Illig; T Meitinger; E Org; A Pfeufer; HE Wichmann; S Kathiresan; J Marrugat; CJ O'Donnell; SM Schwartz; DS Siscovick; I Subirana; NB Freimer; AL Hartikainen; MI McCarthy; PF O'Reilly; L Peltonen; A Pouta; Jong PE de; H Snieder; Gilst WH van; R Clarke; A Goel; A Hamsten; JF Peden; U Seedorf; AC Syvänen; G Tognoni; EG Lakatta; S Sanna; P Scheet; D Schlessinger; A Scuteri; M Dörr; F Ernst; SB Felix; G Homuth; R Lorbeer; T Reffelmann; R Rettig; U Völker; P Galan; IG Gut; S Hercberg; GM Lathrop; D Zeleneka; P Deloukas; N Soranzo; FM Williams; G Zhai; V Salomaa; M Laakso; R Elosua; NG Forouhi; H Völzke; CS Uiterwaal; der Schouw YT van; ME Numans; MATULLO Giuseppe; G Navis; G Berglund; SA Bingham; JS Kooner; JM Connell; S Bandinelli; L Ferrucci; H Watkins; TD Spector; J Tuomilehto; D Altshuler; DP Strachan; M Laan; P Meneton; NJ Wareham; M Uda; MR Jarvelin; V Mooser; O Melander; RJ Loos; P Elliott; GR Abecasis; M Caulfield; PB Munroe

doi:10.1161/HYPERTENSIONAHA.110.153429

Common variants in the ATP2B1 gene are associated with susceptibility to hypertension: the Japanese Millennium Genome Project

Y Tabara, K Kohara, Y Kita, N Hirawa, T Katsuya, T Ohkubo, Y Hiura, A Tajima, T Morisaki, T Miyata, T Nakayama, N Takashima, J Nakura, R Kawamoto, N Takahashi, A Hata, M Soma, Y Imai, Y Kokubo, T OkamuraH Tomoike, N Iwai, T Ogihara, I Inoue, K Tokunaga, T Johnson, M Caulfield, P Munroe, Global Blood Pressure Genetics Consortium, S Umemura, H Ueshima, T. Collaborators: Newton Cheh C Miki, T Johnson, V Gateva, MD Tobin, M Bochud, L Coin, SS Najjar, JH Zhao, SC Heath, S Eyheramendy, K Papadakis, BF Voight, LJ Scott, F Zhang, M Farrall, T Tanaka, C Wallace, JC Chambers, KT Khaw, P Nilsson, der Harst P van, Silvia POLIDORO, DE Grobbee, Moret NC Onland, ML Bots, LV Wain, KS Elliott, A Teumer, J Luan, G Lucas, J Kuusisto, PR Burton, D Hadley, WL McArdle, M Brown, A Dominiczak, SJ Newhouse, NJ Samani, J Webster, E Zeggini, JS Beckmann, S Bergmann, N Lim, K Song, P Vollenweider, G Waeber, DM Waterworth, X Yuan, L Groop, Melander M Orho, A Allione, ALESSANDRA DI GREGORIO, GUARRERA Simonetta, S Panico, FULVIO RICCERI, VALERIA ROMANAZZI, Carlotta SACERDOTE, VINEIS Paolo, I Barroso, MS Sandhu, RN Luben, GJ Crawford, P Jousilahti, M Perola, M Boehnke, LL Bonnycastle, FS Collins, AU Jackson, KL Mohlke, HM Stringham, TT Valle, CJ Willer, RN Bergman, MA Morken, A Döring, C Gieger, T Illig, T Meitinger, E Org, A Pfeufer, HE Wichmann, S Kathiresan, J Marrugat, CJ O'Donnell, SM Schwartz, DS Siscovick, I Subirana, NB Freimer, AL Hartikainen, MI McCarthy, PF O'Reilly, L Peltonen, A Pouta, Jong PE de, H Snieder, Gilst WH van, R Clarke, A Goel, A Hamsten, JF Peden, U Seedorf, AC Syvänen, G Tognoni, EG Lakatta, S Sanna, P Scheet, D Schlessinger, A Scuteri, M Dörr, F Ernst, SB Felix, G Homuth, R Lorbeer, T Reffelmann, R Rettig, U Völker, P Galan, IG Gut, S Hercberg, GM Lathrop, D Zeleneka, P Deloukas, N Soranzo, FM Williams, G Zhai, V Salomaa, M Laakso, R Elosua, NG Forouhi, H Völzke, CS Uiterwaal, der Schouw YT van, ME Numans, MATULLO Giuseppe, G Navis, G Berglund, SA Bingham, JS Kooner, JM Connell, S Bandinelli, L Ferrucci, H Watkins, TD Spector, J Tuomilehto, D Altshuler, DP Strachan, M Laan, P Meneton, NJ Wareham, M Uda, MR Jarvelin, V Mooser, O Melander, RJ Loos, P Elliott, GR Abecasis, M Caulfield, PB Munroe

Risultato della ricerca: Contributo su rivista › Articolo in rivista › peer review

Abstract

Hypertension is one of the most common complex genetic disorders. We have described previously 38 single nucleotide polymorphisms (SNPs) with suggestive association with hypertension in Japanese individuals. In this study we extend our previous findings by analyzing a large sample of Japanese individuals (n=14 105) for the most associated SNPs. We also conducted replication analyses in Japanese of susceptibility loci for hypertension identified recently from genome-wide association studies of European ancestries. Association analysis revealed significant association of the ATP2B1 rs2070759 polymorphism with hypertension (P=5.3×10(-5); allelic odds ratio: 1.17 [95% CI: 1.09 to 1.26]). Additional SNPs in ATP2B1 were subsequently genotyped, and the most significant association was with rs11105378 (odds ratio: 1.31 [95% CI: 1.21 to 1.42]; P=4.1×10(-11)). Association of rs11105378 with hypertension was cross-validated by replication analysis with the Global Blood Pressure Genetics consortium data set (odds ratio: 1.13 [95% CI: 1.05 to 1.21]; P=5.9×10(-4)). Mean adjusted systolic blood pressure was highly significantly associated with the same SNP in a meta-analysis with individuals of European descent (P=1.4×10(-18)). ATP2B1 mRNA expression levels in umbilical artery smooth muscle cells were found to be significantly different among rs11105378 genotypes. Seven SNPs discovered in published genome-wide association studies were also genotyped in the Japanese population. In the combined analysis with replicated 3 genes, FGF5 rs1458038, CYP17A1, rs1004467, and CSK rs1378942, odds ratio of the highest risk group was 2.27 (95% CI: 1.65 to 3.12; P=4.6×10(-7)) compared with the lower risk group. In summary, this study confirmed common genetic variation in ATP2B1, as well as FGF5, CYP17A1, and CSK, to be associated with blood pressure levels and risk of hypertension

Lingua originale	Inglese
pagine (da-a)	973-980
Numero di pagine	8
Rivista	Hypertension
Volume	56
Numero di pubblicazione	5
DOI	https://doi.org/10.1161/HYPERTENSIONAHA.110.153429
Stato di pubblicazione	Pubblicato - 2010

Keywords

hypertension
genetic variation
ATP2B1
Millenium Genome Project
Global BPgen

Accesso al documento

10.1161/HYPERTENSIONAHA.110.153429

Altri file e collegamenti

handle

Cita questo

Tabara, Y., Kohara, K., Kita, Y., Hirawa, N., Katsuya, T., Ohkubo, T., Hiura, Y., Tajima, A., Morisaki, T., Miyata, T., Nakayama, T., Takashima, N., Nakura, J., Kawamoto, R., Takahashi, N., Hata, A., Soma, M., Imai, Y., Kokubo, Y., ... Munroe, PB. (2010). Common variants in the ATP2B1 gene are associated with susceptibility to hypertension: the Japanese Millennium Genome Project. Hypertension, 56(5), 973-980. https://doi.org/10.1161/HYPERTENSIONAHA.110.153429

@article{e6c127bef1ea4694ba0a4ad0e173fb33,

title = "Common variants in the ATP2B1 gene are associated with susceptibility to hypertension: the Japanese Millennium Genome Project",

abstract = "Hypertension is one of the most common complex genetic disorders. We have described previously 38 single nucleotide polymorphisms (SNPs) with suggestive association with hypertension in Japanese individuals. In this study we extend our previous findings by analyzing a large sample of Japanese individuals (n=14 105) for the most associated SNPs. We also conducted replication analyses in Japanese of susceptibility loci for hypertension identified recently from genome-wide association studies of European ancestries. Association analysis revealed significant association of the ATP2B1 rs2070759 polymorphism with hypertension (P=5.3×10(-5); allelic odds ratio: 1.17 [95% CI: 1.09 to 1.26]). Additional SNPs in ATP2B1 were subsequently genotyped, and the most significant association was with rs11105378 (odds ratio: 1.31 [95% CI: 1.21 to 1.42]; P=4.1×10(-11)). Association of rs11105378 with hypertension was cross-validated by replication analysis with the Global Blood Pressure Genetics consortium data set (odds ratio: 1.13 [95% CI: 1.05 to 1.21]; P=5.9×10(-4)). Mean adjusted systolic blood pressure was highly significantly associated with the same SNP in a meta-analysis with individuals of European descent (P=1.4×10(-18)). ATP2B1 mRNA expression levels in umbilical artery smooth muscle cells were found to be significantly different among rs11105378 genotypes. Seven SNPs discovered in published genome-wide association studies were also genotyped in the Japanese population. In the combined analysis with replicated 3 genes, FGF5 rs1458038, CYP17A1, rs1004467, and CSK rs1378942, odds ratio of the highest risk group was 2.27 (95% CI: 1.65 to 3.12; P=4.6×10(-7)) compared with the lower risk group. In summary, this study confirmed common genetic variation in ATP2B1, as well as FGF5, CYP17A1, and CSK, to be associated with blood pressure levels and risk of hypertension",

keywords = "hypertension, genetic variation, ATP2B1, Millenium Genome Project, Global BPgen, hypertension, genetic variation, ATP2B1, Millenium Genome Project, Global BPgen",

author = "Y Tabara and K Kohara and Y Kita and N Hirawa and T Katsuya and T Ohkubo and Y Hiura and A Tajima and T Morisaki and T Miyata and T Nakayama and N Takashima and J Nakura and R Kawamoto and N Takahashi and A Hata and M Soma and Y Imai and Y Kokubo and T Okamura and H Tomoike and N Iwai and T Ogihara and I Inoue and K Tokunaga and T Johnson and M Caulfield and P Munroe and Consortium, {Global Blood Pressure Genetics} and S Umemura and H Ueshima and Miki, {T. Collaborators: Newton Cheh C} and T Johnson and V Gateva and MD Tobin and M Bochud and L Coin and SS Najjar and JH Zhao and SC Heath and S Eyheramendy and K Papadakis and BF Voight and LJ Scott and F Zhang and M Farrall and T Tanaka and C Wallace and JC Chambers and KT Khaw and P Nilsson and van, {der Harst P} and Silvia POLIDORO and DE Grobbee and Onland, {Moret NC} and ML Bots and LV Wain and KS Elliott and A Teumer and J Luan and G Lucas and J Kuusisto and PR Burton and D Hadley and WL McArdle and M Brown and A Dominiczak and SJ Newhouse and NJ Samani and J Webster and E Zeggini and JS Beckmann and S Bergmann and N Lim and K Song and P Vollenweider and G Waeber and DM Waterworth and X Yuan and L Groop and Orho, {Melander M} and A Allione and {DI GREGORIO}, ALESSANDRA and GUARRERA Simonetta and S Panico and FULVIO RICCERI and VALERIA ROMANAZZI and Carlotta SACERDOTE and VINEIS Paolo and I Barroso and MS Sandhu and RN Luben and GJ Crawford and P Jousilahti and M Perola and M Boehnke and LL Bonnycastle and FS Collins and AU Jackson and KL Mohlke and HM Stringham and TT Valle and CJ Willer and RN Bergman and MA Morken and A D{\"o}ring and C Gieger and T Illig and T Meitinger and E Org and A Pfeufer and HE Wichmann and S Kathiresan and J Marrugat and CJ O'Donnell and SM Schwartz and DS Siscovick and I Subirana and NB Freimer and AL Hartikainen and MI McCarthy and PF O'Reilly and L Peltonen and A Pouta and de, {Jong PE} and H Snieder and van, {Gilst WH} and R Clarke and A Goel and A Hamsten and JF Peden and U Seedorf and AC Syv{\"a}nen and G Tognoni and EG Lakatta and S Sanna and P Scheet and D Schlessinger and A Scuteri and M D{\"o}rr and F Ernst and SB Felix and G Homuth and R Lorbeer and T Reffelmann and R Rettig and U V{\"o}lker and P Galan and IG Gut and S Hercberg and GM Lathrop and D Zeleneka and P Deloukas and N Soranzo and FM Williams and G Zhai and V Salomaa and M Laakso and R Elosua and NG Forouhi and H V{\"o}lzke and CS Uiterwaal and van, {der Schouw YT} and ME Numans and MATULLO Giuseppe and G Navis and G Berglund and SA Bingham and JS Kooner and JM Connell and S Bandinelli and L Ferrucci and H Watkins and TD Spector and J Tuomilehto and D Altshuler and DP Strachan and M Laan and P Meneton and NJ Wareham and M Uda and MR Jarvelin and V Mooser and O Melander and RJ Loos and P Elliott and GR Abecasis and M Caulfield and PB Munroe",

year = "2010",

doi = "10.1161/HYPERTENSIONAHA.110.153429",

language = "English",

volume = "56",

pages = "973--980",

journal = "Hypertension",

issn = "0194-911X",

publisher = "Lippincott Williams and Wilkins",

number = "5",

}

Tabara, Y, Kohara, K, Kita, Y, Hirawa, N, Katsuya, T, Ohkubo, T, Hiura, Y, Tajima, A, Morisaki, T, Miyata, T, Nakayama, T, Takashima, N, Nakura, J, Kawamoto, R, Takahashi, N, Hata, A, Soma, M, Imai, Y, Kokubo, Y, Okamura, T, Tomoike, H, Iwai, N, Ogihara, T, Inoue, I, Tokunaga, K, Johnson, T, Caulfield, M, Munroe, P, Consortium, GBPG, Umemura, S, Ueshima, H, Miki, TCNCC, Johnson, T, Gateva, V, Tobin, MD, Bochud, M, Coin, L, Najjar, SS, Zhao, JH, Heath, SC, Eyheramendy, S, Papadakis, K, Voight, BF, Scott, LJ, Zhang, F, Farrall, M, Tanaka, T, Wallace, C, Chambers, JC, Khaw, KT, Nilsson, P, van, DHP, POLIDORO, S, Grobbee, DE, Onland, MNC, Bots, ML, Wain, LV, Elliott, KS, Teumer, A, Luan, J, Lucas, G, Kuusisto, J, Burton, PR, Hadley, D, McArdle, WL, Brown, M, Dominiczak, A, Newhouse, SJ, Samani, NJ, Webster, J, Zeggini, E, Beckmann, JS, Bergmann, S, Lim, N, Song, K, Vollenweider, P, Waeber, G, Waterworth, DM, Yuan, X, Groop, L, Orho, MM, Allione, A, DI GREGORIO, ALESSANDRA, Simonetta, GUARRERA, Panico, S, RICCERI, FULVIO, ROMANAZZI, VALERIA, SACERDOTE, C, Paolo, VINEIS, Barroso, I, Sandhu, MS, Luben, RN, Crawford, GJ, Jousilahti, P, Perola, M, Boehnke, M, Bonnycastle, LL, Collins, FS, Jackson, AU, Mohlke, KL, Stringham, HM, Valle, TT, Willer, CJ, Bergman, RN, Morken, MA, Döring, A, Gieger, C, Illig, T, Meitinger, T, Org, E, Pfeufer, A, Wichmann, HE, Kathiresan, S, Marrugat, J, O'Donnell, CJ, Schwartz, SM, Siscovick, DS, Subirana, I, Freimer, NB, Hartikainen, AL, McCarthy, MI, O'Reilly, PF, Peltonen, L, Pouta, A, de, JPE, Snieder, H, van, GWH, Clarke, R, Goel, A, Hamsten, A, Peden, JF, Seedorf, U, Syvänen, AC, Tognoni, G, Lakatta, EG, Sanna, S, Scheet, P, Schlessinger, D, Scuteri, A, Dörr, M, Ernst, F, Felix, SB, Homuth, G, Lorbeer, R, Reffelmann, T, Rettig, R, Völker, U, Galan, P, Gut, IG, Hercberg, S, Lathrop, GM, Zeleneka, D, Deloukas, P, Soranzo, N, Williams, FM, Zhai, G, Salomaa, V, Laakso, M, Elosua, R, Forouhi, NG, Völzke, H, Uiterwaal, CS, van, DSYT, Numans, ME, Giuseppe, MATULLO, Navis, G, Berglund, G, Bingham, SA, Kooner, JS, Connell, JM, Bandinelli, S, Ferrucci, L, Watkins, H, Spector, TD, Tuomilehto, J, Altshuler, D, Strachan, DP, Laan, M, Meneton, P, Wareham, NJ, Uda, M, Jarvelin, MR, Mooser, V, Melander, O, Loos, RJ, Elliott, P, Abecasis, GR, Caulfield, M & Munroe, PB 2010, 'Common variants in the ATP2B1 gene are associated with susceptibility to hypertension: the Japanese Millennium Genome Project', Hypertension, vol. 56, n. 5, pagg. 973-980. https://doi.org/10.1161/HYPERTENSIONAHA.110.153429

TY - JOUR

T1 - Common variants in the ATP2B1 gene are associated with susceptibility to hypertension: the Japanese Millennium Genome Project

AU - Tabara, Y

AU - Kohara, K

AU - Kita, Y

AU - Hirawa, N

AU - Katsuya, T

AU - Ohkubo, T

AU - Hiura, Y

AU - Tajima, A

AU - Morisaki, T

AU - Miyata, T

AU - Nakayama, T

AU - Takashima, N

AU - Nakura, J

AU - Kawamoto, R

AU - Takahashi, N

AU - Hata, A

AU - Soma, M

AU - Imai, Y

AU - Kokubo, Y

AU - Okamura, T

AU - Tomoike, H

AU - Iwai, N

AU - Ogihara, T

AU - Inoue, I

AU - Tokunaga, K

AU - Johnson, T

AU - Caulfield, M

AU - Munroe, P

AU - Consortium, Global Blood Pressure Genetics

AU - Umemura, S

AU - Ueshima, H

AU - Miki, T. Collaborators: Newton Cheh C

AU - Johnson, T

AU - Gateva, V

AU - Tobin, MD

AU - Bochud, M

AU - Coin, L

AU - Najjar, SS

AU - Zhao, JH

AU - Heath, SC

AU - Eyheramendy, S

AU - Papadakis, K

AU - Voight, BF

AU - Scott, LJ

AU - Zhang, F

AU - Farrall, M

AU - Tanaka, T

AU - Wallace, C

AU - Chambers, JC

AU - Khaw, KT

AU - Nilsson, P

AU - van, der Harst P

AU - POLIDORO, Silvia

AU - Grobbee, DE

AU - Onland, Moret NC

AU - Bots, ML

AU - Wain, LV

AU - Elliott, KS

AU - Teumer, A

AU - Luan, J

AU - Lucas, G

AU - Kuusisto, J

AU - Burton, PR

AU - Hadley, D

AU - McArdle, WL

AU - Brown, M

AU - Dominiczak, A

AU - Newhouse, SJ

AU - Samani, NJ

AU - Webster, J

AU - Zeggini, E

AU - Beckmann, JS

AU - Bergmann, S

AU - Lim, N

AU - Song, K

AU - Vollenweider, P

AU - Waeber, G

AU - Waterworth, DM

AU - Yuan, X

AU - Groop, L

AU - Orho, Melander M

AU - Allione, A

AU - DI GREGORIO, ALESSANDRA

AU - Simonetta, GUARRERA

AU - Panico, S

AU - RICCERI, FULVIO

AU - ROMANAZZI, VALERIA

AU - SACERDOTE, Carlotta

AU - Paolo, VINEIS

AU - Barroso, I

AU - Sandhu, MS

AU - Luben, RN

AU - Crawford, GJ

AU - Jousilahti, P

AU - Perola, M

AU - Boehnke, M

AU - Bonnycastle, LL

AU - Collins, FS

AU - Jackson, AU

AU - Mohlke, KL

AU - Stringham, HM

AU - Valle, TT

AU - Willer, CJ

AU - Bergman, RN

AU - Morken, MA

AU - Döring, A

AU - Gieger, C

AU - Illig, T

AU - Meitinger, T

AU - Org, E

AU - Pfeufer, A

AU - Wichmann, HE

AU - Kathiresan, S

AU - Marrugat, J

AU - O'Donnell, CJ

AU - Schwartz, SM

AU - Siscovick, DS

AU - Subirana, I

AU - Freimer, NB

AU - Hartikainen, AL

AU - McCarthy, MI

AU - O'Reilly, PF

AU - Peltonen, L

AU - Pouta, A

AU - de, Jong PE

AU - Snieder, H

AU - van, Gilst WH

AU - Clarke, R

AU - Goel, A

AU - Hamsten, A

AU - Peden, JF

AU - Seedorf, U

AU - Syvänen, AC

AU - Tognoni, G

AU - Lakatta, EG

AU - Sanna, S

AU - Scheet, P

AU - Schlessinger, D

AU - Scuteri, A

AU - Dörr, M

AU - Ernst, F

AU - Felix, SB

AU - Homuth, G

AU - Lorbeer, R

AU - Reffelmann, T

AU - Rettig, R

AU - Völker, U

AU - Galan, P

AU - Gut, IG

AU - Hercberg, S

AU - Lathrop, GM

AU - Zeleneka, D

AU - Deloukas, P

AU - Soranzo, N

AU - Williams, FM

AU - Zhai, G

AU - Salomaa, V

AU - Laakso, M

AU - Elosua, R

AU - Forouhi, NG

AU - Völzke, H

AU - Uiterwaal, CS

AU - van, der Schouw YT

AU - Numans, ME

AU - Giuseppe, MATULLO

AU - Navis, G

AU - Berglund, G

AU - Bingham, SA

AU - Kooner, JS

AU - Connell, JM

AU - Bandinelli, S

AU - Ferrucci, L

AU - Watkins, H

AU - Spector, TD

AU - Tuomilehto, J

AU - Altshuler, D

AU - Strachan, DP

AU - Laan, M

AU - Meneton, P

AU - Wareham, NJ

AU - Uda, M

AU - Jarvelin, MR

AU - Mooser, V

AU - Melander, O

AU - Loos, RJ

AU - Elliott, P

AU - Abecasis, GR

AU - Caulfield, M

AU - Munroe, PB

PY - 2010

Y1 - 2010

N2 - Hypertension is one of the most common complex genetic disorders. We have described previously 38 single nucleotide polymorphisms (SNPs) with suggestive association with hypertension in Japanese individuals. In this study we extend our previous findings by analyzing a large sample of Japanese individuals (n=14 105) for the most associated SNPs. We also conducted replication analyses in Japanese of susceptibility loci for hypertension identified recently from genome-wide association studies of European ancestries. Association analysis revealed significant association of the ATP2B1 rs2070759 polymorphism with hypertension (P=5.3×10(-5); allelic odds ratio: 1.17 [95% CI: 1.09 to 1.26]). Additional SNPs in ATP2B1 were subsequently genotyped, and the most significant association was with rs11105378 (odds ratio: 1.31 [95% CI: 1.21 to 1.42]; P=4.1×10(-11)). Association of rs11105378 with hypertension was cross-validated by replication analysis with the Global Blood Pressure Genetics consortium data set (odds ratio: 1.13 [95% CI: 1.05 to 1.21]; P=5.9×10(-4)). Mean adjusted systolic blood pressure was highly significantly associated with the same SNP in a meta-analysis with individuals of European descent (P=1.4×10(-18)). ATP2B1 mRNA expression levels in umbilical artery smooth muscle cells were found to be significantly different among rs11105378 genotypes. Seven SNPs discovered in published genome-wide association studies were also genotyped in the Japanese population. In the combined analysis with replicated 3 genes, FGF5 rs1458038, CYP17A1, rs1004467, and CSK rs1378942, odds ratio of the highest risk group was 2.27 (95% CI: 1.65 to 3.12; P=4.6×10(-7)) compared with the lower risk group. In summary, this study confirmed common genetic variation in ATP2B1, as well as FGF5, CYP17A1, and CSK, to be associated with blood pressure levels and risk of hypertension

AB - Hypertension is one of the most common complex genetic disorders. We have described previously 38 single nucleotide polymorphisms (SNPs) with suggestive association with hypertension in Japanese individuals. In this study we extend our previous findings by analyzing a large sample of Japanese individuals (n=14 105) for the most associated SNPs. We also conducted replication analyses in Japanese of susceptibility loci for hypertension identified recently from genome-wide association studies of European ancestries. Association analysis revealed significant association of the ATP2B1 rs2070759 polymorphism with hypertension (P=5.3×10(-5); allelic odds ratio: 1.17 [95% CI: 1.09 to 1.26]). Additional SNPs in ATP2B1 were subsequently genotyped, and the most significant association was with rs11105378 (odds ratio: 1.31 [95% CI: 1.21 to 1.42]; P=4.1×10(-11)). Association of rs11105378 with hypertension was cross-validated by replication analysis with the Global Blood Pressure Genetics consortium data set (odds ratio: 1.13 [95% CI: 1.05 to 1.21]; P=5.9×10(-4)). Mean adjusted systolic blood pressure was highly significantly associated with the same SNP in a meta-analysis with individuals of European descent (P=1.4×10(-18)). ATP2B1 mRNA expression levels in umbilical artery smooth muscle cells were found to be significantly different among rs11105378 genotypes. Seven SNPs discovered in published genome-wide association studies were also genotyped in the Japanese population. In the combined analysis with replicated 3 genes, FGF5 rs1458038, CYP17A1, rs1004467, and CSK rs1378942, odds ratio of the highest risk group was 2.27 (95% CI: 1.65 to 3.12; P=4.6×10(-7)) compared with the lower risk group. In summary, this study confirmed common genetic variation in ATP2B1, as well as FGF5, CYP17A1, and CSK, to be associated with blood pressure levels and risk of hypertension

KW - hypertension

KW - genetic variation

KW - ATP2B1

KW - Millenium Genome Project

KW - Global BPgen

KW - hypertension

KW - genetic variation

KW - ATP2B1

KW - Millenium Genome Project

KW - Global BPgen

UR - https://iris.uniupo.it/handle/null

U2 - 10.1161/HYPERTENSIONAHA.110.153429

DO - 10.1161/HYPERTENSIONAHA.110.153429

M3 - Article

SN - 0194-911X

VL - 56

SP - 973

EP - 980

JO - Hypertension

JF - Hypertension

IS - 5

ER -

Common variants in the ATP2B1 gene are associated with susceptibility to hypertension: the Japanese Millennium Genome Project

Abstract

Keywords

Accesso al documento

Altri file e collegamenti

Fingerprint

Cita questo