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Association of genetic variants with dyslipidemia and chronic kidney disease in a longitudinal population-based genetic epidemiological study.

Yamada Y, Matsui K, Takeuchi I, Fujimaki T - Int. J. Mol. Med. (2015)

Bottom Line: 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).

View Article: PubMed Central - PubMed

Affiliation: Department of Human Functional Genomics, Life Science Research Center, Mie University, Tsu, Mie 514‑8507, Japan.

ABSTRACT
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.

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Longitudinal analysis of the association between the prevalence of (A) hypertriglyceridemia or (B) hyper-low-density lipoprotein (LDL) cholesterolemia and age with a generalized estimating equation, or between the serum concentrations of (C) triglycerides or (D) LDL cholesterol and age with a generalized linear mixed-effect model, according to the genotype for rs6929846 of butyrophilin, subfamily 2, member A1 gene (BTN2A1) (CT + TT vs. CC).
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f1-ijmm-35-05-1290: Longitudinal analysis of the association between the prevalence of (A) hypertriglyceridemia or (B) hyper-low-density lipoprotein (LDL) cholesterolemia and age with a generalized estimating equation, or between the serum concentrations of (C) triglycerides or (D) LDL cholesterol and age with a generalized linear mixed-effect model, according to the genotype for rs6929846 of butyrophilin, subfamily 2, member A1 gene (BTN2A1) (CT + TT vs. CC).

Mentions: The association between the prevalence of hypertriglyceridemia or hyper-LDL cholesterolemia and age was analyzed longitudinally with a generalized estimating equation according to the BTN2A1 genotype. The prevalence of hypertriglyceridemia (Fig. 1A) or hyper-LDL cholesterolemia (Fig. 1B) was greater in the combined group of subjects with the CT or TT genotypes of rs6929846 of BTN2A1 than in the subjects with the CC genotype from 40 to 90 years of age. The association between the serum concentrations of triglycerides or LDL cholesterol with age was also analyzed longitudinally according to the BTN2A1 genotype in all individuals with a generalized linear mixed-effect model. The serum concentrations of triglycerides (Fig. 1C) or LDL cholesterol (Fig. 1D) were greater in the combined group of individuals with the CT or TT genotypes of rs6929846 of BTN2A1 than in those with the CC genotype from 40 to 90 years of age.


Association of genetic variants with dyslipidemia and chronic kidney disease in a longitudinal population-based genetic epidemiological study.

Yamada Y, Matsui K, Takeuchi I, Fujimaki T - Int. J. Mol. Med. (2015)

Longitudinal analysis of the association between the prevalence of (A) hypertriglyceridemia or (B) hyper-low-density lipoprotein (LDL) cholesterolemia and age with a generalized estimating equation, or between the serum concentrations of (C) triglycerides or (D) LDL cholesterol and age with a generalized linear mixed-effect model, according to the genotype for rs6929846 of butyrophilin, subfamily 2, member A1 gene (BTN2A1) (CT + TT vs. CC).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4380205&req=5

f1-ijmm-35-05-1290: Longitudinal analysis of the association between the prevalence of (A) hypertriglyceridemia or (B) hyper-low-density lipoprotein (LDL) cholesterolemia and age with a generalized estimating equation, or between the serum concentrations of (C) triglycerides or (D) LDL cholesterol and age with a generalized linear mixed-effect model, according to the genotype for rs6929846 of butyrophilin, subfamily 2, member A1 gene (BTN2A1) (CT + TT vs. CC).
Mentions: The association between the prevalence of hypertriglyceridemia or hyper-LDL cholesterolemia and age was analyzed longitudinally with a generalized estimating equation according to the BTN2A1 genotype. The prevalence of hypertriglyceridemia (Fig. 1A) or hyper-LDL cholesterolemia (Fig. 1B) was greater in the combined group of subjects with the CT or TT genotypes of rs6929846 of BTN2A1 than in the subjects with the CC genotype from 40 to 90 years of age. The association between the serum concentrations of triglycerides or LDL cholesterol with age was also analyzed longitudinally according to the BTN2A1 genotype in all individuals with a generalized linear mixed-effect model. The serum concentrations of triglycerides (Fig. 1C) or LDL cholesterol (Fig. 1D) were greater in the combined group of individuals with the CT or TT genotypes of rs6929846 of BTN2A1 than in those with the CC genotype from 40 to 90 years of age.

Bottom Line: 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).

View Article: PubMed Central - PubMed

Affiliation: Department of Human Functional Genomics, Life Science Research Center, Mie University, Tsu, Mie 514‑8507, Japan.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus