Association Of DOCK7-ANGPTL3 Single Nucleotide Polymorphims With Serum Lipid Levels And The Risk Of Coronary Disease And Ischemic Stroke

Objective: According to recent Genome-wide association study,single nucleotide polymorphisms(SNPs)in DOCK7 and ANGPTL3 gene was associated with serum lipid,the risk of coronary artery disease(CAD)or ischemic stroke(IS),but such association wasn't detect about SNPs in DOCK7-ANGPTL3 gene in a Southern Chinese Han population.Our present study aim to detect the associations between DOCK7-ANGPTL3 SNPs with the serum lipid levels and the risk of coronary artery disease and ischemic stroke in Guangxi Han population.methods : the present study was conceived as a case-control study in which1728 Guangxi Han population participants contains(controls,621;CAD,568;IS,539).Information about all the subjects was got by standardizedquestionnaires and venous blood sample was obtained.Genotype of the DOCK7rs1748195 and ANGPTL3 rs12563308 were determined by the Snapshot technology platform.results : There were different frequencies of genotype and allele of DOCK7 rs1748195 between CAD and controls(P<0.05).CAD patients' rs1748195 G allele frequency was higher than controls'(27.6% vs.23.6%,P=0.024).Genotype frequency of ANGPTL3 rs12563308 in CAD was different from that of controls(P =0.021).After controlling potential risk factors and Bonferroni correction was employed,rs1748195 G allele was associated with the risk of CAD(Recessive: OR = 1.79,95%CI = 1.04-3.06,P = 0.017;Log-additive: OR = 1.27,95%CI = 1.02-1.57,P = 0.014)and rs12563308 was associated with the risk of CAD(Dominant: OR = 0.69,95%CI = 0.45-0.94,P =0.011;Log-additive: OR = 0.73,95%CI = 0.49-0.89,P = 0.009).There was association between rs1748195 SNP and the severity to coronary artery atherosclerosis(CAS;Dominant: OR = 1.45,95%CI = 1.07-2.11,P = 0.017;Log-additive: OR = 1.35,95%CI = 1.09-1.82,P = 0.013).Interactions of gene and environmental risk factors on the serum lipid levels,the severity to coronary artery atherosclerosis and the risk of CAD and IS were detected in our present study.rs1748195G-12563308 T haplotype was associated with an increased risk of CAS and CAD compared to rs1748195C-12563308 T haplotype(CAS:OR=1.46,95%CI=1.05-2.03;P =0.023;CAD: OR=1.37,95%CI=1.08-1.74,P=0.009).Analysis of haplotype interacted with environmental risk factors onthe risk of CAD and IS showed that rs1748195C-rs12563308T/rs1748195Grs12563308 T haplotypes interacted with hypertension(yes)associated with an increased risk of CAD(C-T: OR=2.98,95%CI=2.07-4.30;G-T: OR=2.49,95%CI=1.66-3.74).For the normotensive participants,haplotype of rs1748195G-rs12563308 T was associated with an increased risk of CAD(OR=1.47,95%CI=1.09-1.99).As compared with their own same haplotypes,the rs1748195G-rs12563308 T and rs1748195G-rs12563308 C interacted with drinking both were associated with decrease risk of CAD than non-drinkers(G-T: OR=0.71,95%CI=0.36-0.89;G-C: OR=0.26,95%CI=0.11-0.58).As compared with non-drinkers,rs1748195G-rs12563308 T /rs1748195G-rs12563308 C interacted with alcohol consumption decrease the risk of IS(G-T: OR=0.38,95%CI=0.23-0.61;G-C: OR=0.24,95%CI=0.10-0.55).Respectively,rs1748195G-rs1256 3308 T was associated with an increased risk of CAD compared to rs1748195C-rs12563308 T haplotype in non-drinkers.Conclusions: Our present study showed that single nucleotide polymorphisms in DOCK7-ANGPTL3 gene and their haplotypes were associated with the angiographic severity to coronary artery atherosclerosis and the risk of CAD and IS in the Guangxi Han population.Homozygote of rs1748195 GG was associated with an increased risk of CAD compared to rs1748195 C allele carrier,whereas rs12563308 C allele carrier was associated with a decrease risk of CAD compared to rs12563308 TT homozygote.rs1748195G-rs12563308 T haplotypewas associated with an increased risk of CAD compared to rs1748195C-rs12563308 T haplotype.rs1748195 G allele carrier(compared to rs1748195 CC hemozygote)and rs1748195G-12563308 T haplotype(compared to rs1748195C-12563308 T haplotype)were associated with increased risk of angiographic severity to coronary artery atherosclerosis.DOCK7-ANGPTL3 SNPs and their haplotypes interacted with environment(sex,alcohol consumption,smoking,hypertension,BMI;respectively)influence the serum lipid levels,the angiographic severity of coronary atherosclerosis in CAD and the risk of CAD and IS.