刘继斌
中国医学科学院阜外医院
VKORC1 genetic polymorphisms affect warfarin dose response, aortic calcification, and the susceptibility of coronary artery disease as shown in our previous study. Little is known regarding the association of VKORC1 polymorphisms with coronary artery calcification (CAC) and the role of CAC in the association with coronary artery disease (CAD). Due to a natural haplotype block in the VKORC1 gene in Chinese, polymorphism rs2359612 was analyzed in a case-control study and a prospective study. The case-control study included 464 CAD patients with non-calcified plaque (NCP), 562 CAD patients with mixed calcified plaque (MCP), 492 subjects with calcified plaque (CP), and 521 controls. The rs2359612C was only associated with increased risk of MCP, the CAD in the presence of CAC; the odds ratio was 1.397 (95 % CI 1.008-1.937, P < 0.05), which was replicated in the second independent population. On the contrary, a negative correlation was observed between rs2359612 and log-transformed Agatston score, and rs2359612 was negatively associated with the number of calcified vessels. Moreover, in a prospective study including 849 CAD patients undergoing revascularization, rs2359612C predicted a higher incidence of cardiovascular events in MCP subgroup; the relative risk was 1.435 (95 % CI 1.008-2.041, P = 0.045), which was not observed in the NCP subgroup. We conclude that the rs2359612C was associated with a higher risk of CAD in the presence of CAC and a higher incidence of cardiovascular events in CAD patients with CAC, but a lower coronary calcification. VKORC1 polymorphisms may be associated with the endophenotype of CAD, calcification-related atherosclerosis.
Human genetics 2013
BACKGROUND:Vitronectin is involved in the whole process of atherosclerosis. Our aim is to determine the association of VTN functional promoter variants with different types of vascular disease, and conclude the roles of vitronectin involved in vascular disease.METHODS:Gel shift assays and luciferase reporter assays were used to determine the impact of variants on promoter activity. The correlation of plasma vitronectin levels with the variant was assessed in normal controls. The association of the variant with vascular disease was determined in 3 case-control studies.RESULTS:A strong linkage disequilibrium was found between rs2227721 and rs2227720 in VTN promoter in Chinese (r(2)=1.0). Both variants resulted in a decreased transcription activity, and rs2227721 decreased the binding efficiency of transcription factor YY1 to the region. The rs2227721 was correlated with plasma vitronectin levels in normal controls (r=-0.207, P=0.028). The rs2227721 was associated with susceptibility of vascular disease; the odds ratios among subjects carrying rs2227721-T allele were 1.298 (95% Confidence Interval-CI, 1.033-1.631) for non-MI CAD (P<0.05), 1.346 (95% CI, 1.068-1.695) for chronic MI (P<0.05), 1.486 (95% CI, 1.145-1.928) for acute MI (P<0.001), and 1.619 (95% CI, 1.108-2.366) for deep venous thrombosis (P<0.05).CONCLUSION:VTN promoter haplotype would be a novel genetic marker for vascular disease.
International journal of cardiology 2013
BACKGROUND AND PURPOSE:ANRIL encodes a long antisense noncoding RNA in the INK4 locus. Although ANRIL has been proven to be associated with coronary heart disease, its roles in stroke are inconsistent, and sparse data are available regarding hemorrhagic stroke.METHODS:A Chinese case-control study was conducted, comprising 1657 cases (724 atherothrombosis, 466 lacunar infarction, and 462 hemorrhagic strokes) and 1664 controls. Stroke patients were prospectively followed-up for a median of 4.5 (range, 0.1-6.0) years. Expression of ANRIL transcripts was examined in 42 human atherosclerotic plaques.RESULTS:After adjustment for vascular risk factors and correction for multiple comparisons, subjects carrying the GG genotype of rs10757278 had 1.47-fold (95% CI, 1.11-1.89; P=0.05) and 1.60-fold (95% CI, 1.16-2.15; P=0.04) increased risk for atherothrombotic and hemorrhagic strokes, respectively. During the follow-up, 317 recurrent strokes and 301 deaths from all causes were documented. Subjects carrying rs10757278GG had higher risk for stroke recurrence (relative risk [RR],1.56; 95% CI,1.15-2.12; P=0.005) and cardiovascular mortality (RR, 2.0; 95% CI, 1.26-3.18; P=0.003), respectively. Rs10757274 was also associated with stroke risk and recurrence. Family history of stroke further increased the stroke risk by 2.37-fold (95% CI, 1.38-4.06; P=0.01) and recurrent stroke risk by 2.45-fold (95% CI, 1.56-3.86; P<0.0001) respectively, when compared with those carrying none of G-alleles and without family history. Finally, rs10757278 was associated with differential expression of the ANRIL transcripts.CONCLUSIONS:Our findings indicated that the ANRIL may serve as a novel genetic marker for the risk of atherothrombotic and hemorrhagic stroke and their recurrence.
Stroke 2012
