Han BG

References (2)

Title : Carriage of the V279F null allele within the gene encoding Lp-PLA(2) is protective from coronary artery disease in South Korean males - Jang_2011_PLoS.One_6_e18208
Author(s) : Jang Y , Waterworth D , Lee JE , Song K , Kim S , Kim HS , Park KW , Cho HJ , Oh IY , Park JE , Lee BS , Ku HJ , Shin DJ , Lee JH , Jee SH , Han BG , Jang HY , Cho EY , Vallance P , Whittaker J , Cardon L , Mooser V
Ref : PLoS ONE , 6 :e18208 , 2011
Abstract : BACKGROUND: The Asia-specific PLA2G7 994G-T transversion leads to V279F substitution within the lipoprotein-associated phospholipase-A2 (Lp-PLA(2)) and to absence of enzyme activity in plasma. This variant offers a unique natural experiment to assess the role of Lp-PLA(2) in the pathogenesis of coronary artery disease (CAD) in humans. Given conflicting results from mostly small studies, a large two-stage case-control study was warranted. METHODOLOGY/PRINCIPAL FINDINGS: PLA2G7 V279F genotypes were initially compared in 2890 male cases diagnosed with CAD before age 60 with 3128 male controls without CAD at age 50 and above and subsequently in a second independent male dataset of 877 CAD cases and 1230 controls. In the first dataset, the prevalence of the 279F null allele was 11.5% in cases and 12.8% in controls. After adjustment for age, body mass index, diabetes, smoking, glucose and lipid levels, the OR (95% CI) for CAD for this allele was 0.80 (0.66-0.97, p = 0.02). The results were very similar in the second dataset, despite lower power, with an allele frequency of 11.2% in cases and 12.5% in controls, leading to a combined OR of 0.80 (0.69-0.92), p = 0.002. The magnitude and direction of this genetic effect were fully consistent with large epidemiological studies on plasma Lp-PLA(2) activity and CAD risk.
CONCLUSIONS: Natural deficiency in Lp-PLA(2) activity due to carriage of PLA2G7 279F allele protects from CAD in Korean men. These results provide evidence for a causal relationship between Lp-PLA(2) and CAD, and support pharmacological inhibition of this enzyme as an innovative way to prevent CAD.
ESTHER : Jang_2011_PLoS.One_6_e18208
PubMedSearch : Jang_2011_PLoS.One_6_e18208
PubMedID: 21490708
Gene_locus related to this paper: human-PLA2G7

Title : Association of lipoprotein lipase (LPL) single nucleotide polymorphisms with type 2 diabetes mellitus - Cho_2008_Exp.Mol.Med_40_523
Author(s) : Cho YS , Go MJ , Han HR , Cha SH , Kim HT , Min H , Shin HD , Park C , Han BG , Cho NH , Shin C , Kimm K , Oh B
Ref : Exp Mol Med , 40 :523 , 2008
Abstract : The etiology and pathogenesis of type 2 diabetes mellitus (T2DM) are not completely understood although it is often associated with other conditions such as obesity, hypertension, and dyslipidemia. Lipoprotein lipase (LPL) is a key enzyme in human lipid metabolism that facilitates the removal of triglyceride-rich lipoproteins from the bloodstream. LPL hydrolyzes the core of triglyceride-rich lipoproteins (chylomicrons and very low density lipoprotein) into free fatty acids and monoacylglycerol. To gain insight into the possible role of LPL in T2DM, nine single nucleotide polymorphisms (SNPs) of LPL were analyzed for the association with T2DM using 944 unrelated Koreans, including 474 T2DM subjects and 470 normal healthy controls. Of the nine LPL SNPs we analyzed, a significant association with multiple tests by the false discovery rate (FDR) was observed between T2DM and SNP rs343 (+13836C>A in intron 3). SNP rs343 was also marginally associated with some of T2DM-related phenotypes including total cholesterol, high density lipoprotein cholesterol (HDLc), and log transformed glycosylated hemoglobin in 470 normal controls, although no significant association was detected by multiple tests. In total, our results suggest that the control of lipid level by LPL in the bloodstream might be an important factor in T2DM pathogenesis in the Korean population.
ESTHER : Cho_2008_Exp.Mol.Med_40_523
PubMedSearch : Cho_2008_Exp.Mol.Med_40_523
PubMedID: 18985010