TY - JOUR
T1 - Common variants in the ATP2B1 gene are associated with susceptibility to hypertension
T2 - The Japanese millennium genome project
AU - Tabara, Yasuharu
AU - Kohara, Katsuhiko
AU - Kita, Yoshikuni
AU - Hirawa, Nobuhito
AU - Katsuya, Tomohiro
AU - Ohkubo, Takayoshi
AU - Hiura, Yumiko
AU - Tajima, Atsushi
AU - Morisaki, Takayuki
AU - Miyata, Toshiyuki
AU - Nakayama, Tomohiro
AU - Takashima, Naoyuki
AU - Nakura, Jun
AU - Kawamoto, Ryuichi
AU - Takahashi, Norio
AU - Hata, Akira
AU - Soma, Masayoshi
AU - Imai, Yutaka
AU - Kokubo, Yoshihiro
AU - Okamura, Tomonori
AU - Tomoike, Hitonobu
AU - Iwai, Naoharu
AU - Ogihara, Toshio
AU - Inoue, Itsuro
AU - Tokunaga, Katsushi
AU - Johnson, Toby
AU - Caulfield, Mark
AU - Munroe, Patricia
AU - Umemura, Satoshi
AU - Ueshima, Hirotsugu
AU - Miki, Tetsuro
PY - 2010/11/1
Y1 - 2010/11/1
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; 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). 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). 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). 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) 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; 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). 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). 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). 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) 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 - Millennium Genome Project
KW - genetic variation
KW - hypertension
UR - http://www.scopus.com/inward/record.url?scp=78049531165&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78049531165&partnerID=8YFLogxK
U2 - 10.1161/HYPERTENSIONAHA.110.153429
DO - 10.1161/HYPERTENSIONAHA.110.153429
M3 - Article
C2 - 20921432
AN - SCOPUS:78049531165
SN - 0194-911X
VL - 56
SP - 973
EP - 980
JO - Hypertension
JF - Hypertension
IS - 5
ER -