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

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

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

ATP2B1
Global BPgen
Millenium Genome Project
genetic variation
hypertension

Accesso al documento

10.1161/HYPERTENSIONAHA.110.153429

https://hdl.handle.net/11579/223162

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., ... PB, M. (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 = "ATP2B1, Global BPgen, Millenium Genome Project, genetic variation, hypertension, ATP2B1, Global BPgen, Millenium Genome Project, genetic variation, hypertension",

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

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, MD, T, Bochud, M, Coin, L, SS, N, JH, Z, SC, H, Eyheramendy, S, Papadakis, K, BF, V, LJ, S, Zhang, F, Farrall, M, Tanaka, T, Wallace, C, JC, C, KT, K, Nilsson, P, van der Harst, P, POLIDORO, S, DE, G, NC, OM, ML, B, LV, W, KS, E, Teumer, A, Luan, J, Lucas, G, Kuusisto, J, PR, B, Hadley, D, WL, M, Brown, M, Dominiczak, A, SJ, N, NJ, S, Webster, J, Zeggini, E, JS, B, Bergmann, S, Lim, N, Song, K, Vollenweider, P, Waeber, G, DM, W, Yuan, X, Groop, L, Orho, MM, Allione, A, DI GREGORIO, ALESSANDRA, GUARRERA, S, Panico, S, RICCERI, FULVIO, ROMANAZZI, VALERIA, SACERDOTE, C, VINEIS, P, Barroso, I, MS, S, RN, L, GJ, C, Jousilahti, P, Perola, M, Boehnke, M, LL, B, FS, C, AU, J, KL, M, HM, S, TT, V, CJ, W, RN, B, MA, M, Döring, A, Gieger, C, Illig, T, Meitinger, T, Org, E, Pfeufer, A, HE, W, Kathiresan, S, Marrugat, J, CJ, OD, SM, S, DS, S, Subirana, I, NB, F, AL, H, MI, M, PF, OR, Peltonen, L, Pouta, A, PE, DJ, Snieder, H, WH, VG, Clarke, R, Goel, A, Hamsten, A, JF, P, Seedorf, U, AC, S, Tognoni, G, EG, L, Sanna, S, Scheet, P, Schlessinger, D, Scuteri, A, Dörr, M, Ernst, F, SB, F, Homuth, G, Lorbeer, R, Reffelmann, T, Rettig, R, Völker, U, Galan, P, IG, G, Hercberg, S, GM, L, Zeleneka, D, Deloukas, P, Soranzo, N, FM, W, Zhai, G, Salomaa, V, Laakso, M, Elosua, R, NG, F, Völzke, H, CS, U, YT, VDS, ME, N, MATULLO, G, Navis, G, Berglund, G, SA, B, JS, K, JM, C, Bandinelli, S, Ferrucci, L, Watkins, H, TD, S, Tuomilehto, J, Altshuler, D, DP, S, Laan, M, Meneton, P, NJ, W, Uda, M, MR, J, Mooser, V, Melander, O, RJ, L, Elliott, P, GR, A, Caulfield, M & PB, M 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 - MD, Tobin

AU - Bochud, M

AU - Coin, L

AU - SS, Najjar

AU - JH, Zhao

AU - SC, Heath

AU - Eyheramendy, S

AU - Papadakis, K

AU - BF, Voight

AU - LJ, Scott

AU - Zhang, F

AU - Farrall, M

AU - Tanaka, T

AU - Wallace, C

AU - JC, Chambers

AU - KT, Khaw

AU - Nilsson, P

AU - van der Harst, P

AU - POLIDORO, Silvia

AU - DE, Grobbee

AU - NC, Onland Moret

AU - ML, Bots

AU - LV, Wain

AU - KS, Elliott

AU - Teumer, A

AU - Luan, J

AU - Lucas, G

AU - Kuusisto, J

AU - PR, Burton

AU - Hadley, D

AU - WL, McArdle

AU - Brown, M

AU - Dominiczak, A

AU - SJ, Newhouse

AU - NJ, Samani

AU - Webster, J

AU - Zeggini, E

AU - JS, Beckmann

AU - Bergmann, S

AU - Lim, N

AU - Song, K

AU - Vollenweider, P

AU - Waeber, G

AU - DM, Waterworth

AU - Yuan, X

AU - Groop, L

AU - Orho, Melander M

AU - Allione, A

AU - DI GREGORIO, ALESSANDRA

AU - GUARRERA, Simonetta

AU - Panico, S

AU - RICCERI, FULVIO

AU - ROMANAZZI, VALERIA

AU - SACERDOTE, Carlotta

AU - VINEIS, Paolo

AU - Barroso, I

AU - MS, Sandhu

AU - RN, Luben

AU - GJ, Crawford

AU - Jousilahti, P

AU - Perola, M

AU - Boehnke, M

AU - LL, Bonnycastle

AU - FS, Collins

AU - AU, Jackson

AU - KL, Mohlke

AU - HM, Stringham

AU - TT, Valle

AU - CJ, Willer

AU - RN, Bergman

AU - MA, Morken

AU - Döring, A

AU - Gieger, C

AU - Illig, T

AU - Meitinger, T

AU - Org, E

AU - Pfeufer, A

AU - HE, Wichmann

AU - Kathiresan, S

AU - Marrugat, J

AU - CJ, O'Donnell

AU - SM, Schwartz

AU - DS, Siscovick

AU - Subirana, I

AU - NB, Freimer

AU - AL, Hartikainen

AU - MI, McCarthy

AU - PF, O'Reilly

AU - Peltonen, L

AU - Pouta, A

AU - PE, de Jong

AU - Snieder, H

AU - WH, van Gilst

AU - Clarke, R

AU - Goel, A

AU - Hamsten, A

AU - JF, Peden

AU - Seedorf, U

AU - AC, Syvänen

AU - Tognoni, G

AU - EG, Lakatta

AU - Sanna, S

AU - Scheet, P

AU - Schlessinger, D

AU - Scuteri, A

AU - Dörr, M

AU - Ernst, F

AU - SB, Felix

AU - Homuth, G

AU - Lorbeer, R

AU - Reffelmann, T

AU - Rettig, R

AU - Völker, U

AU - Galan, P

AU - IG, Gut

AU - Hercberg, S

AU - GM, Lathrop

AU - Zeleneka, D

AU - Deloukas, P

AU - Soranzo, N

AU - FM, Williams

AU - Zhai, G

AU - Salomaa, V

AU - Laakso, M

AU - Elosua, R

AU - NG, Forouhi

AU - Völzke, H

AU - CS, Uiterwaal

AU - YT, van der Schouw

AU - ME, Numans

AU - MATULLO, Giuseppe

AU - Navis, G

AU - Berglund, G

AU - SA, Bingham

AU - JS, Kooner

AU - JM, Connell

AU - Bandinelli, S

AU - Ferrucci, L

AU - Watkins, H

AU - TD, Spector

AU - Tuomilehto, J

AU - Altshuler, D

AU - DP, Strachan

AU - Laan, M

AU - Meneton, P

AU - NJ, Wareham

AU - Uda, M

AU - MR, Jarvelin

AU - Mooser, V

AU - Melander, O

AU - RJ, Loos

AU - Elliott, P

AU - GR, Abecasis

AU - Caulfield, M

AU - PB, Munroe

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 - ATP2B1

KW - Global BPgen

KW - Millenium Genome Project

KW - genetic variation

KW - hypertension

KW - ATP2B1

KW - Global BPgen

KW - Millenium Genome Project

KW - genetic variation

KW - hypertension

UR - https://iris.uniupo.it/handle/11579/223162

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

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