Palmen J

References (3)

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 : Investigation into the role of the hormone sensitive lipase -60C>G promoter variant in morbid obesity - Talmud_2005_Nutr.Metab.Cardiovasc.Dis_15_31
Author(s) : Talmud PJ , Palmen J , Wolf AM , Beisiegel U
Ref : Nutr Metab Cardiovasc Dis , 15 :31 , 2005
Abstract : BACKGROUND: Hormone sensitive lipase (HSL) plays a central role in free fatty acid homeostasis in adipose tissue and in pancreatic beta-cells, where it contributes to the control of insulin secretion by generating long-chain fatty acids. AIM: We examined the frequency and association of the functional HSL promoter variant, -60C>G, in a German cohort of morbidly obese women (N=239) and men (N=55) and compared the frequency to a cohort of 199 blood donors, recruited from the same region.
RESULTS: The rare allele frequency of -60C>G, in the obese individuals was significantly lower 0.031 (95% CI 0.02, 0.04), than that in the blood donors 0.061 (95% CI 0.04, 0.08) p=0.05. The association of the HSL -60C>G with lipid and glucose parameters was examined in the obese women (there were too few men for comparative analysis). In the obese women, those heterozygous for the -60G had significantly higher glucose levels compared to CC women, 142.71 (+/-16.23) mg/dl vs. 110.34 (+/-1.79) mg/dl, respectively (p=0.0001). There was no statistically significant difference in other parameters. CONCLUSION: This study confirms a role for HSL in glucose homeostasis and the reduced frequency of the low expressing -60G promoter variant in obese individuals, together with existing published data, suggests that this allele might be protective against obesity.
ESTHER : Talmud_2005_Nutr.Metab.Cardiovasc.Dis_15_31
PubMedSearch : Talmud_2005_Nutr.Metab.Cardiovasc.Dis_15_31
PubMedID: 15871848

Title : Familial lipoprotein lipase (LPL) deficiency: a catalogue of LPL gene mutations identified in 20 patients from the UK, Sweden, and Italy - Mailly_1997_Hum.Mutat_10_465
Author(s) : Mailly F , Palmen J , Muller DP , Gibbs T , Lloyd J , Brunzell J , Durrington P , Mitropoulos K , Betteridge J , Watts G , Lithell H , Angelico F , Humphries SE , Talmud PJ
Ref : Hum Mutat , 10 :465 , 1997
Abstract : The aim of this study was to identify mutations in the lipoprotein lipase (LPL) gene in 20 unrelated patients with familial lipoprotein deficiency (FLLD) and to investigate the genotype/phenotype relationship. The previously reported G188E mutation (Monsalve et al., J Clin Invest 86:728-734, 1990) was screened for and found to be present in seven individuals (12/40 alleles). In addition, three patients were heterozygous for the 2.0 kb insertion (Langlois et al., Proc Nalt Acad Sci US 86:948-952, 1989). Two approaches were taken for new mutation detection; single-strand conformation polymorphism and sequencing to identify micro-mutations in the proximal promoter and exons 1-9 of the LPL gene and Southern blotting to identify gross mutations. Ten different point mutations were found (W86G, A158T, H183Q, G188E, S193R, P207L, L252X, N291S, M301T, L303P). Additionally, a two nucleotide deletion in exon 6 (delta1006-1007), a six nucleotide deletion in exon 8 (delta1441-1447), and a silent substitution in the wobble position of codon E118 were identified. In vitro mutagenesis and expression in COS-B cells suggested that the A158T and S193R substitutions virtually abolished enzyme activity. In analysing the genotype/phenotype relationship, there was no strong association between age at diagnosis, severity of symptoms, lipid levels, and the nature/position of the mutation. Triglyceride levels, however, were higher in compound heterozygotes compared to true homozygotes, possibly reflecting increased instability of heterodimers. Overall, 29 of 40 (72.5%) mutant alleles were identified. Failure to identify the mutation in 11 alleles might reflect the inadequacy of the method or the possibility that mutations lie within regions of the gene not screened in the study because of lack of availability of sequence.
ESTHER : Mailly_1997_Hum.Mutat_10_465
PubMedSearch : Mailly_1997_Hum.Mutat_10_465
PubMedID: 9401010