Dataset Information

Association of genetic variants with coronary artery disease and ischemic stroke in a longitudinal population-based genetic epidemiological study.

ABSTRACT: Our previous studies identified nine genes and chromosomal region 3q28 as susceptibility loci for myocardial infarction, ischemic stroke or chronic kidney disease by genome-wide or candidate gene association studies. As coronary artery disease (CAD) and ischemic stroke may share genetic architecture, certain genetic variants may confer susceptibility to the two diseases. The present study examined the association of 13 polymorphisms at these 10 loci with the prevalence of CAD or ischemic stroke in community-dwelling individuals, with the aim of identifying genetic variants that confer susceptibility to the two conditions. Study subjects (170 with CAD, 117 with ischemic stroke and 5,718 controls) were recruited to the Inabe Health and Longevity Study, a longitudinal genetic epidemiological study of atherosclerotic, cardiovascular and metabolic diseases. The subjects were recruited from individuals who visited for an annual health checkup and they were followed up each year (mean follow-up period, 5 years). Longitudinal analysis with a generalized estimating equation, and with adjustment for age, gender, body mass index, smoking status, the prevalence of hypertension, diabetes mellitus and dyslipidemia and the serum concentration of creatinine, revealed that rs2074380 (G?A) and rs2074381 (A?G) of the ?-kinase 1 (ALPK1) gene and rs8089 (T?G) of the thrombospondin 2 (THBS2) gene were significantly (P<2×10-16) associated with the prevalence of CAD, with the AA genotype of rs2074380 and GG genotypes of rs2074381 and rs8089 being protective against this condition. Similar analysis revealed that rs9846911 (A?G) at chromosome 3q28, rs2074381 of ALPK1, rs8089 of THBS2 and rs6046 (G?A) of the coagulation factor VII gene were significantly (P<2×10-16) associated with the prevalence of ischemic stroke, with the GG genotypes of rs9846911, rs2074381 and rs8089 and the AA genotype of rs6046 being protective against this condition. ALPK1 and THBS2 may thus be susceptibility loci for CAD and ischemic stroke.

SUBMITTER: Yamada Y

PROVIDER: S-EPMC4461855 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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Association of genetic variants with coronary artery disease and ischemic stroke in a longitudinal population-based genetic epidemiological study.

Yamada Yoshiji Y Matsui Kota K Takeuchi Ichiro I Fujimaki Tetsuo T

Biomedical reports 20150302 3

Our previous studies identified nine genes and chromosomal region 3q28 as susceptibility loci for myocardial infarction, ischemic stroke or chronic kidney disease by genome-wide or candidate gene association studies. As coronary artery disease (CAD) and ischemic stroke may share genetic architecture, certain genetic variants may confer susceptibility to the two diseases. The present study examined the association of 13 polymorphisms at these 10 loci with the prevalence of CAD or ischemic stroke ...[more]

PMID: 26137247

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Project description:We previously identified 9 genes and chromosomal region 3q28 as susceptibility loci for Japanese patients with myocardial infarction, ischemic stroke, or chronic kidney disease by genome-wide or candidate gene association studies. In the present study, we investigated the possible association of 13 single nucleotide polymorphisms (SNPs) at these 10 loci with the prevalence of hypertension or their association with blood pressure (BP) in community-dwelling individuals in Japan. The study subjects comprised 6,027 individuals (2,250 subjects with essential hypertension, 3,777 controls) who were recruited into the Inabe Health and Longevity Study, a longitudinal genetic epidemiological study on atherosclerotic, cardiovascular and metabolic diseases. The subjects were recruited from individuals who visited the Health Care Center of Inabe General Hospital for an annual health checkup, and they are followed up each year (mean follow?up period, 5 years). Longitudinal analysis with a generalized estimating equation and with adjustment for age, gender, body mass index and smoking status revealed that rs2116519 of family with sequence similarity 78, member B (FAM78B; P=0.0266), rs6929846 of butyrophilin, subfamily 2, member A1 (BTN2A1; P=0.0013), rs146021107 of pancreatic and duodenal homeobox 1 (PDX1; P=0.0031) and rs1671021 of lethal giant larvae homolog 2 (Drosophila) (LLGL2; P=0.0372) were significantly (P<0.05) associated with the prevalence of hypertension. Longitudinal analysis with a generalized linear mixed-effect model and with adjustment for age, gender, body mass index and smoking status among individuals not taking anti-hypertensive medication revealed that rs6929846 of BTN2A1 was significantly associated with systolic (P=0.0017), diastolic (P=0.0008) and mean (P=0.0005) BP, and that rs2116519 of FAM78B, rs146021107 of PDX1 and rs1671021 of LLGL2 were significantly associated with diastolic (P=0.0495), systolic (P=0.0132), and both diastolic (P=0.0468) and mean (0.0471) BP, respectively. BTN2A1 may thus be a susceptibility gene for hypertension.

Project description:We previously identified 9 genes and chromosomal region 3q28 as susceptibility loci for myocardial infarction, ischemic stroke, or chronic kidney disease (CKD) in Japanese individuals by genome-wide or candidate gene association studies. In the present study, we examined the association of 13 polymorphisms at these 10 loci with the prevalence of hypertriglyceridemia, hyper-low-density lipoprotein (LDL) cholesterolemia, hypo-high-density lipoprotein (HDL) cholesterolemia, or CKD in community-dwelling Japanese individuals. The study subjects comprised 6,027 individuals who were recruited to the Inabe Health and Longevity Study, a longitudinal genetic epidemiological study of atherosclerotic, cardiovascular and metabolic diseases. The subjects were recruited from individuals who visited the Health Care Center at Inabe General Hospital for an annual health checkup, and they were followed up each year (mean follow?up period, 5 years). Longitudinal analysis with a generalized estimating equation and with adjustment for covariates revealed that rs6929846 of butyrophilin, subfamily 2, member A1 gene (BTN2A1) was significantly associated with the prevalence of hypertriglyceridemia (P=0.0001), hyper-LDL cholesterolemia (P=0.0004), and CKD (P=0.0007); rs2569512 of interleukin enhancer binding factor 3 (ILF3) was associated with hyper-LDL cholesterolemia (P=0.0029); and rs2074379 (P=0.0019) and rs2074388 (P=0.0029) of alpha-kinase 1 (ALPK1) were associated with CKD. Longitudinal analysis with a generalized linear mixed-effect model and with adjustment for covariates among all individuals revealed that rs6929846 of BTN2A1 was significantly associated with the serum concentrations of triglycerides (P=0.0011), LDL cholesterol (P=3.3 x 10(-5)), and creatinine (P=0.0006), as well as with the estimated glomerular filtration rate (eGFR) (P=0.0004); rs2569512 of ILF3 was shown to be associated with the serum concentration of LDL cholesterol (P=0.0221); and rs2074379 (P=0.0302) and rs2074388 (P=0.0336) of ALPK1 were shown to be associated with the serum concentration of creatinine. Similar analysis among individuals not taking any anti?dyslipidemic medication revealed that rs6929846 of BTN2A1 was significantly associated with the serum concentrations of triglycerides (P=8.3 x 10?5) and LDL cholesterol (P=0.0004), and that rs2569512 of ILF3 was associated with the serum concentration of LDL cholesterol (P=0.0010). BTN2A1 may thus be a susceptibility gene for hypertriglyceridemia, hyper?LDL cholesterolemia and CKD in Japanese individuals.

Dataset Information

Association of genetic variants with coronary artery disease and ischemic stroke in a longitudinal population-based genetic epidemiological study.

Publications

Association of genetic variants with coronary artery disease and ischemic stroke in a longitudinal population-based genetic epidemiological study.

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