The Val279Phe variant of the lipoprotein-associated phospholipase A2 gene is associated with catalytic activities and cardiovascular disease in Korean men

Yangsoo Jang, Yoen Kim Oh, Jeong Koh Soo, Sook Chae Jey, Guk Ko Young, Young Kim Ji, Hongkeun Cho, Tae Sook Jeong, Song Lee Woo, Jose M. Ordovas, Jong Ho Lee

Research output: Contribution to journalArticle

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Abstract

Context and Objective: It is unclear whether lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ) exerts a pro- or antiatherogenic effect on cardiovascular disease (CVD). We investigated the association between Lp-PLA 2 variant (V279F and A379V) and CVD in Korean men. Design: CVD patients (n = 532) and healthy controls (n = 670) were genotyped for the Lp-PLA 2 polymorphism (V279F and A379V). Main Outcome Measures: We calculated odds ratio (OR) on CVD risk and measured anthropometries, lipid profiles, low-density lipoprotein (LDL) particle size, oxidized LDL, lipid peroxides, and Lp-PLA 2 activity. Results: The presence of the 279F allele was associated with a lower risk of CVD [OR 0.646 (95% confidence interval 0.490-0.850), P = 0.002], and the association still remained after adjustments for age, body mass index, waist circumference, waist to hip ratio, cigarette smoking, and alcohol consumption [OR 0.683 (95% confidence interval 0.512-0.911), P = 0.009]. Lp-PLA 2 activity was lower in CVD patients taking a lipid-lowering drug (31%), those not taking a lipid-lowering drug (26%), and control subjects (23%) with the V/F genotype, compared with those with the V/V genotype. Subjects with the F/F genotype in controls and two CVD patients groups showed no appreciable enzymatic activity. Control subjects with the V/F genotype had larger LDL particle size than those with the V/V genotype. In addition, control subjects carrying the F allele showed lower malondialdehyde concentrations. On the other hand, we found no significant relationship between A379V genotype and CVD risk. Conclusions: The association of the F279 loss of function variant with the reduced risk of CVD supports the concept that Lp-PLA 2 plays a proatherogenic and causative role in CVD.

Original languageEnglish
Pages (from-to)3521-3527
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume91
Issue number9
DOIs
Publication statusPublished - 2006 Jan 1

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1-Alkyl-2-acetylglycerophosphocholine Esterase
Catalyst activity
Cardiovascular Diseases
Genes
Genotype
Odds Ratio
Lipids
LDL Lipoproteins
Particle Size
Alleles
Particle size
Anthropometry
Confidence Intervals
Waist-Hip Ratio
Lipid Peroxides
Drug and Narcotic Control
Waist Circumference
Malondialdehyde
Polymorphism
Tobacco Products

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Jang, Yangsoo ; Oh, Yoen Kim ; Soo, Jeong Koh ; Jey, Sook Chae ; Young, Guk Ko ; Ji, Young Kim ; Cho, Hongkeun ; Jeong, Tae Sook ; Woo, Song Lee ; Ordovas, Jose M. ; Lee, Jong Ho. / The Val279Phe variant of the lipoprotein-associated phospholipase A2 gene is associated with catalytic activities and cardiovascular disease in Korean men. In: Journal of Clinical Endocrinology and Metabolism. 2006 ; Vol. 91, No. 9. pp. 3521-3527.
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abstract = "Context and Objective: It is unclear whether lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ) exerts a pro- or antiatherogenic effect on cardiovascular disease (CVD). We investigated the association between Lp-PLA 2 variant (V279F and A379V) and CVD in Korean men. Design: CVD patients (n = 532) and healthy controls (n = 670) were genotyped for the Lp-PLA 2 polymorphism (V279F and A379V). Main Outcome Measures: We calculated odds ratio (OR) on CVD risk and measured anthropometries, lipid profiles, low-density lipoprotein (LDL) particle size, oxidized LDL, lipid peroxides, and Lp-PLA 2 activity. Results: The presence of the 279F allele was associated with a lower risk of CVD [OR 0.646 (95{\%} confidence interval 0.490-0.850), P = 0.002], and the association still remained after adjustments for age, body mass index, waist circumference, waist to hip ratio, cigarette smoking, and alcohol consumption [OR 0.683 (95{\%} confidence interval 0.512-0.911), P = 0.009]. Lp-PLA 2 activity was lower in CVD patients taking a lipid-lowering drug (31{\%}), those not taking a lipid-lowering drug (26{\%}), and control subjects (23{\%}) with the V/F genotype, compared with those with the V/V genotype. Subjects with the F/F genotype in controls and two CVD patients groups showed no appreciable enzymatic activity. Control subjects with the V/F genotype had larger LDL particle size than those with the V/V genotype. In addition, control subjects carrying the F allele showed lower malondialdehyde concentrations. On the other hand, we found no significant relationship between A379V genotype and CVD risk. Conclusions: The association of the F279 loss of function variant with the reduced risk of CVD supports the concept that Lp-PLA 2 plays a proatherogenic and causative role in CVD.",
author = "Yangsoo Jang and Oh, {Yoen Kim} and Soo, {Jeong Koh} and Jey, {Sook Chae} and Young, {Guk Ko} and Ji, {Young Kim} and Hongkeun Cho and Jeong, {Tae Sook} and Woo, {Song Lee} and Ordovas, {Jose M.} and Lee, {Jong Ho}",
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The Val279Phe variant of the lipoprotein-associated phospholipase A2 gene is associated with catalytic activities and cardiovascular disease in Korean men. / Jang, Yangsoo; Oh, Yoen Kim; Soo, Jeong Koh; Jey, Sook Chae; Young, Guk Ko; Ji, Young Kim; Cho, Hongkeun; Jeong, Tae Sook; Woo, Song Lee; Ordovas, Jose M.; Lee, Jong Ho.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 91, No. 9, 01.01.2006, p. 3521-3527.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The Val279Phe variant of the lipoprotein-associated phospholipase A2 gene is associated with catalytic activities and cardiovascular disease in Korean men

AU - Jang, Yangsoo

AU - Oh, Yoen Kim

AU - Soo, Jeong Koh

AU - Jey, Sook Chae

AU - Young, Guk Ko

AU - Ji, Young Kim

AU - Cho, Hongkeun

AU - Jeong, Tae Sook

AU - Woo, Song Lee

AU - Ordovas, Jose M.

AU - Lee, Jong Ho

PY - 2006/1/1

Y1 - 2006/1/1

N2 - Context and Objective: It is unclear whether lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ) exerts a pro- or antiatherogenic effect on cardiovascular disease (CVD). We investigated the association between Lp-PLA 2 variant (V279F and A379V) and CVD in Korean men. Design: CVD patients (n = 532) and healthy controls (n = 670) were genotyped for the Lp-PLA 2 polymorphism (V279F and A379V). Main Outcome Measures: We calculated odds ratio (OR) on CVD risk and measured anthropometries, lipid profiles, low-density lipoprotein (LDL) particle size, oxidized LDL, lipid peroxides, and Lp-PLA 2 activity. Results: The presence of the 279F allele was associated with a lower risk of CVD [OR 0.646 (95% confidence interval 0.490-0.850), P = 0.002], and the association still remained after adjustments for age, body mass index, waist circumference, waist to hip ratio, cigarette smoking, and alcohol consumption [OR 0.683 (95% confidence interval 0.512-0.911), P = 0.009]. Lp-PLA 2 activity was lower in CVD patients taking a lipid-lowering drug (31%), those not taking a lipid-lowering drug (26%), and control subjects (23%) with the V/F genotype, compared with those with the V/V genotype. Subjects with the F/F genotype in controls and two CVD patients groups showed no appreciable enzymatic activity. Control subjects with the V/F genotype had larger LDL particle size than those with the V/V genotype. In addition, control subjects carrying the F allele showed lower malondialdehyde concentrations. On the other hand, we found no significant relationship between A379V genotype and CVD risk. Conclusions: The association of the F279 loss of function variant with the reduced risk of CVD supports the concept that Lp-PLA 2 plays a proatherogenic and causative role in CVD.

AB - Context and Objective: It is unclear whether lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ) exerts a pro- or antiatherogenic effect on cardiovascular disease (CVD). We investigated the association between Lp-PLA 2 variant (V279F and A379V) and CVD in Korean men. Design: CVD patients (n = 532) and healthy controls (n = 670) were genotyped for the Lp-PLA 2 polymorphism (V279F and A379V). Main Outcome Measures: We calculated odds ratio (OR) on CVD risk and measured anthropometries, lipid profiles, low-density lipoprotein (LDL) particle size, oxidized LDL, lipid peroxides, and Lp-PLA 2 activity. Results: The presence of the 279F allele was associated with a lower risk of CVD [OR 0.646 (95% confidence interval 0.490-0.850), P = 0.002], and the association still remained after adjustments for age, body mass index, waist circumference, waist to hip ratio, cigarette smoking, and alcohol consumption [OR 0.683 (95% confidence interval 0.512-0.911), P = 0.009]. Lp-PLA 2 activity was lower in CVD patients taking a lipid-lowering drug (31%), those not taking a lipid-lowering drug (26%), and control subjects (23%) with the V/F genotype, compared with those with the V/V genotype. Subjects with the F/F genotype in controls and two CVD patients groups showed no appreciable enzymatic activity. Control subjects with the V/F genotype had larger LDL particle size than those with the V/V genotype. In addition, control subjects carrying the F allele showed lower malondialdehyde concentrations. On the other hand, we found no significant relationship between A379V genotype and CVD risk. Conclusions: The association of the F279 loss of function variant with the reduced risk of CVD supports the concept that Lp-PLA 2 plays a proatherogenic and causative role in CVD.

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