Sandhu MS

References (2)

Title : PLA2G7 genotype, lipoprotein-associated phospholipase A2 activity, and coronary heart disease risk in 10 494 cases and 15 624 controls of European Ancestry - Casas_2010_Circulation_121_2284
Author(s) : Casas JP , Ninio E , Panayiotou A , Palmen J , Cooper JA , Ricketts SL , Sofat R , Nicolaides AN , Corsetti JP , Fowkes FG , Tzoulaki I , Kumari M , Brunner EJ , Kivimaki M , Marmot MG , Hoffmann MM , Winkler K , Marz W , Ye S , Stirnadel HA , Boekholdt SM , Khaw KT , Humphries SE , Sandhu MS , Hingorani AD , Talmud PJ
Ref : Circulation , 121 :2284 , 2010
Abstract : BACKGROUND: Higher lipoprotein-associated phospholipase A(2)(Lp-PLA2) activity is associated with increased risk of coronary heart disease (CHD), making Lp-PLA2 a potential therapeutic target. PLA2G7 variants associated with Lp-PLA2 activity could evaluate whether this relationship is causal. METHODS AND RESULTS: A meta-analysis including a total of 12 studies (5 prospective, 4 case-control, 1 case-only, and 2 cross-sectional studies; n=26 118) was undertaken to examine the association of the following: (1) Lp-PLA2 activity versus cardiovascular biomarkers and risk factors and CHD events (2 prospective studies; n=4884); (2) PLA2G7 single-nucleotide polymorphisms and Lp-PLA2 activity (3 prospective, 2 case-control, 2 cross-sectional studies; up to n=6094); and (3) PLA2G7 single-nucleotide polymorphisms and angiographic coronary artery disease (2 case-control, 1 case-only study; n=4971 cases) and CHD events (5 prospective, 2 case-control studies; n=5523). Lp-PLA2 activity correlated with several CHD risk markers. Hazard ratios for CHD events for the top versus bottom quartile of Lp-PLA2 activity were 1.61 (95% confidence interval, 1.31 to 1.99) and 1.17 (95% confidence interval, 0.91 to 1.51) after adjustment for baseline traits. Of 7 single-nucleotide polymorphisms, rs1051931 (A379V) showed the strongest association with Lp-PLA2 activity, with VV subjects having 7.2% higher activity than AAs. Genotype was not associated with risk markers, angiographic coronary disease (odds ratio, 1.03; 95% confidence interval, 0.80 to 1.32), or CHD events (odds ratio, 0.98; 95% confidence interval, 0.82 to 1.17). CONCLUSIONS: Unlike Lp-PLA2 activity, PLA2G7 variants associated with modest effects on Lp-PLA2 activity were not associated with cardiovascular risk markers, coronary atheroma, or CHD. Larger association studies, identification of single-nucleotide polymorphisms with larger effects, or randomized trials of specific Lp-PLA2 inhibitors are needed to confirm or refute a contributory role for Lp-PLA2 in CHD.
ESTHER : Casas_2010_Circulation_121_2284
PubMedSearch : Casas_2010_Circulation_121_2284
PubMedID: 20479152
Gene_locus related to this paper: human-PLA2G7

Title : Lack of association between common genetic variation in endothelial lipase (LIPG) and the risk for CAD and DVT - Vergeer_2010_Atherosclerosis_211_558
Author(s) : Vergeer M , Cohn DM , Boekholdt SM , Sandhu MS , Prins HM , Ricketts SL , Wareham NJ , Kastelein JJ , Khaw KT , Kamphuisen PW , Dallinga-Thie GM
Ref : Atherosclerosis , 211 :558 , 2010
Abstract : OBJECTIVES: Low levels of high-density lipoprotein cholesterol (HDL-C) are a risk factor for coronary artery disease (CAD) and possibly for deep venous thrombosis (DVT). Endothelial lipase is involved in HDL-C metabolism. Common variants in the endothelial lipase gene (LIPG) have been reported to be associated with HDL-C levels and atherothrombosis, but these findings were not consistent. We determined whether five tagging single nucleotide polymorphisms (SNP) in LIPG were associated with lipid parameters, the risk of CAD and the risk of DVT. METHODS: We used the prospective case-control study nested in the EPIC-Norfolk cohort (1138 CAD cases, 2237 matched controls) for the initial association study and, subsequently, the ACT study (185 patients with documented DVT, 586 patients in which DVT was ruled out) to replicate our findings regarding DVT risk. RESULTS: In EPIC-Norfolk, we found that the minor allele of one SNP, rs2000813 (p.T111I), was associated with moderately higher HDL-C and apolipoprotein A-I levels, higher HDL particle number and larger HDL size. No variants were associated with CAD risk, but three variants were associated with DVT risk (odds ratios 0.60 [95%CI 0.43-0.84], 2.04 [95%CI 1.40-2.98] and 1.67 [95%CI 1.18-2.38] per minor allele for rs2000813, rs6507931 and rs2097055 respectively, p<0.005 for each). However, the association between LIPG SNPs and DVT risk could not be replicated in the ACT study. CONCLUSIONS: Our data support a modest association between the LIPG rs2000813 variant and parameters of HDL metabolism, but no association between common genetic variants in LIPG and CAD or DVT risk.
ESTHER : Vergeer_2010_Atherosclerosis_211_558
PubMedSearch : Vergeer_2010_Atherosclerosis_211_558
PubMedID: 20466371
Gene_locus related to this paper: human-LIPG