title: Genetic variations in ATP2B1, CSK, ARSG and CSMD1 loci are related to blood pressure and/or hypertension in two Korean cohorts.
abstract: Blood pressure, one of the important vital signs, is affected by multiple genetic and environmental factors. Recently, several genome-wide association (GWA) studies have successfully identified genetic factors that influence blood pressure and hypertension risk. In this study, we report results of the Korean Association REsource (KARE, 8842 subjects) GWA study on blood pressure and hypertension risk. In all, 10 single-nucleotide polymorphisms (SNPs) that showed significant association with hypertension were further analysed for replication associations in the Health2 project (7861 subjects). Among these 10 SNPs, 3 were replicated in the Health2 cohort for an association with systolic or diastolic blood pressure. The most significant SNP (rs17249754 located in ATPase, Ca(++) transporting, plasma membrane 1 (ATP2B1)) has been previously reported, and the other two SNPs are rs1378942 in the c-src tyrosine kinase (CSK) gene and rs12945290 in the arylsulphatase G (ARSG) gene. An additional hypertension case-control study confirmed that rs17249754 (in ATP2B1) increases hypertension risk in both the KARE and Health2 (meta-analysis, P-value=4.25 x 10(-9)) cohorts. One more SNP, rs995322, located in the CUB and Sushi multiple domains 1 (CSMD1), is also associated with increased risk of hypertension (meta-analysis, P-value=1.00 x 10(-4)). Despite the difficulty of obtaining replication results for a complex trait genetic association between blood pressure and hypertension, we were able to identify consistent genetic factors in both the Korean cohorts in ATP2B1, CSK, ARSG and CSMD1 genes.
authors: Department of Biomedical Engineering, School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors: K-W
authors: KW
authors: Hong
authors: M J
authors: MJ
authors: Go
authors: H-S
authors: HS
authors: Jin
authors: J-E
authors: JE
authors: Lim
authors: J-Y
authors: JY
authors: Lee
authors: B G
authors: BG
authors: Han
authors: S-Y
authors: SY
authors: Hwang
authors: S-H
authors: SH
authors: Lee
authors: H K
authors: HK
authors: Park
authors: Y S
authors: YS
authors: Cho
authors: B
authors: B
authors: Oh
mesh_terms: D000328:Adult; D000368:Aged; D001192:Arylsulfatases / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D001794:Blood Pressure / Q000235:genetics*; D015992:Body Mass Index; D000081247:CSK Tyrosine-Protein Kinase; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000235:genetics*; D007723:Korea / Q000453:epidemiology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012307:Risk Factors; D025521:Tumor Suppressor Proteins; D019061:src-Family Kinases
chemical_list: C506952:ATP2B1 protein, human; C477880:CSMD1 protein, human; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D025521:Tumor Suppressor Proteins; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human; D001192:Arylsulfatases; D053499:Plasma Membrane Calcium-Transporting ATPases