Objective:To evaluate the influence of–250G>A(rs2070895)polymorphism in hepatic lipase gene(LIPC)promoter on plasma lipid parameters of ischemic stroke patients.Methods:A total of 100 stroke patients and 100 contr...Objective:To evaluate the influence of–250G>A(rs2070895)polymorphism in hepatic lipase gene(LIPC)promoter on plasma lipid parameters of ischemic stroke patients.Methods:A total of 100 stroke patients and 100 control subjects matched for sex(59 men and 41 women)and age were selected.Hepatic lipase activity and lipid profiles were measured while lipoprotein ratios were calculated.Genotyping of the–250G>A promoter polymorphism of the LIPC was performed by the polymerase chain reaction and restriction fragment length polymorphism method combined with 2%gel electrophoresis and then confirmed by direct sequencing.The LIPC promoter gene sequencing data were compared with refseqNG011465.1 LIPC from GenBank.Results:The frequencies of GG,GA and AA genotypes of LIPC rs2070895 polymorphism were 39%,45%and 16%for the control,10%,37%and 53%for the stroke subjects(P<0.0001),respectively.The frequencies of G and A alleles were 61.5%and 38.5%for the control,and 28.5%and 71.5%for the stroke subjects(P<0.0001).Our study shows that the mutant allele of the LIPC promoter was associated with dyslipidemia,lower hepatic lipase activity,and this variation contributed to the increased defective plasma high-density lipoprotein-cholesterol(HDL-C),HDL2-C and HDL3-C concentration for both subjects.The control subjects had 6 single nucleotide polymorphism and 6 amino acid substitutions while the stroke subjects had 32 single nucleotide polymorphism and 20 amino acid substitutions.Conclusions:LIPC–250G>A polymorphism can influence plasma lipid profiles and lipoprotein ratios in patients with ischemic stroke.展开更多
Apolipoprotein(apo) A-V is a novel member of the class of exchangeable apo's involved in triacylglycerol(TG)homeostasis.Whereas a portion of hepatic-derived apoA-V is secreted into plasma and functions to facilit...Apolipoprotein(apo) A-V is a novel member of the class of exchangeable apo's involved in triacylglycerol(TG)homeostasis.Whereas a portion of hepatic-derived apoA-V is secreted into plasma and functions to facilitate lipoprotein Iipase-mediated TG hydrolysis,another portion is recovered intracellularly,in association with cytosolic lipid droplets.Loss of apo A-V function is positively correlated with elevated plasma TG and increased risk of cardiovascular disease.Single nucleotide polymorphisms(SNP) in the APOA5 locus can affect transcription efficiency or introduce deleterious amino acid substitutions.Likewise,rare mutations in APOA5 that compromise functionality are associated with increased plasma TG and premature myocardial infarction.Genetically engineered mouse models and human population studies suggest that,in certain instances,supplementation with wild type(WT) apoA-V may have therapeutic benefit.It is hypothesized that individuals that manifest elevated plasma TG owing to deleterious APOA5 SNPs or rare mutations would respond to WT apoA-V supplementation with improved plasma TG clearance.On the other hand,subjects with hypertriglyceridemia of independent origin(unrelated to apoA-V function) may not respond to apoA-V augmentation in this manner.Improvement in the ability to identify individuals predicted to benefit,advances in gene transfer technology and the strong connection between HTG and heart disease,point to apoA-V supplementation as a viable disease prevention / therapeutic strategy.Candidates would include individuals that manifest chronic TG elevation,have low plasma apoA-V due to an APOA5 mutation/polymorphism and not have deleterious mutations/polymorphisms in other genes known to influence plasma TG levels.展开更多
文摘Objective:To evaluate the influence of–250G>A(rs2070895)polymorphism in hepatic lipase gene(LIPC)promoter on plasma lipid parameters of ischemic stroke patients.Methods:A total of 100 stroke patients and 100 control subjects matched for sex(59 men and 41 women)and age were selected.Hepatic lipase activity and lipid profiles were measured while lipoprotein ratios were calculated.Genotyping of the–250G>A promoter polymorphism of the LIPC was performed by the polymerase chain reaction and restriction fragment length polymorphism method combined with 2%gel electrophoresis and then confirmed by direct sequencing.The LIPC promoter gene sequencing data were compared with refseqNG011465.1 LIPC from GenBank.Results:The frequencies of GG,GA and AA genotypes of LIPC rs2070895 polymorphism were 39%,45%and 16%for the control,10%,37%and 53%for the stroke subjects(P<0.0001),respectively.The frequencies of G and A alleles were 61.5%and 38.5%for the control,and 28.5%and 71.5%for the stroke subjects(P<0.0001).Our study shows that the mutant allele of the LIPC promoter was associated with dyslipidemia,lower hepatic lipase activity,and this variation contributed to the increased defective plasma high-density lipoprotein-cholesterol(HDL-C),HDL2-C and HDL3-C concentration for both subjects.The control subjects had 6 single nucleotide polymorphism and 6 amino acid substitutions while the stroke subjects had 32 single nucleotide polymorphism and 20 amino acid substitutions.Conclusions:LIPC–250G>A polymorphism can influence plasma lipid profiles and lipoprotein ratios in patients with ischemic stroke.
基金Supported by a grant from NIH(R37-HL64159)an AHA Postdoctoral Fellowship Award(VS)
文摘Apolipoprotein(apo) A-V is a novel member of the class of exchangeable apo's involved in triacylglycerol(TG)homeostasis.Whereas a portion of hepatic-derived apoA-V is secreted into plasma and functions to facilitate lipoprotein Iipase-mediated TG hydrolysis,another portion is recovered intracellularly,in association with cytosolic lipid droplets.Loss of apo A-V function is positively correlated with elevated plasma TG and increased risk of cardiovascular disease.Single nucleotide polymorphisms(SNP) in the APOA5 locus can affect transcription efficiency or introduce deleterious amino acid substitutions.Likewise,rare mutations in APOA5 that compromise functionality are associated with increased plasma TG and premature myocardial infarction.Genetically engineered mouse models and human population studies suggest that,in certain instances,supplementation with wild type(WT) apoA-V may have therapeutic benefit.It is hypothesized that individuals that manifest elevated plasma TG owing to deleterious APOA5 SNPs or rare mutations would respond to WT apoA-V supplementation with improved plasma TG clearance.On the other hand,subjects with hypertriglyceridemia of independent origin(unrelated to apoA-V function) may not respond to apoA-V augmentation in this manner.Improvement in the ability to identify individuals predicted to benefit,advances in gene transfer technology and the strong connection between HTG and heart disease,point to apoA-V supplementation as a viable disease prevention / therapeutic strategy.Candidates would include individuals that manifest chronic TG elevation,have low plasma apoA-V due to an APOA5 mutation/polymorphism and not have deleterious mutations/polymorphisms in other genes known to influence plasma TG levels.