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AIM: Chronic heart failure( CHF),caused by ischemic cardiomyopathy( ICM) and nonischemic cardiomyopathy( NICM),is among the leading causes of mortality and morbidity worldwide. Low-density lipoprotein receptor-related protein 6( LRP6) plays a critical role in regulating Wnt signaling. Dysregulated Wnt signaling contributes to high incidence of arrhythmias. Thus,there might be an association between genetic variations of LRP6 and sudden cardiac death( SCD). The objective of the study was to examine the association between common variants of LRP6 and prognosis of CHF patients. METHODS: From July 2005 to December 2009,patients with CHF referred from 10 hospitals and participants without structural heart disease in China were undergone a prospective study. The single-nucleotide polymorphism rs2302684 was selected to evaluate the effect of LRP6 polymorphisms on the survival of the patients. RESULTS: A total of 1 887 patients(1 437 with CHF and 450 in the control group) were finally enrolled for the analysis. During a median follow-up of 61 months,a total of 546(38. 00%) patients died,including 201(36. 81%) cases with SCD and 345(63. 19%) cases with NSCD. No end point event occurred in the control group. Patients carrying A allele of rs2302684 had increased risks of allcause death( P < 0. 01) and SCD( P < 0. 01). After adjusted for the other risk factors,the associations remained significant in allcause death( P < 0. 01) and SCD( P < 0. 01). In patients with CHF caused by ICM,those carrying A allele of rs2302684 also had increased risks of all-cause death( P < 0. 01) and SCD( P < 0. 01). After adjusted for the other risk factors,the associations remained significant in all-cause death( P < 0. 01) and SCD( P < 0. 01). However,there was no association between A allele of rs2302684 and prognosis in patients with CHF caused by NICM. CONCLUSION: The SNP rs2302684 T > A in LRP6 is associated with an increased risk of all-cause death and SCD in patients with CHF in Chinese Han population,and the association is more prevalent in patients with CHF caused by ICM. Thus,LRP6 might be added as a novel predictor of SCD and could provide an attractive and direct therapeutic target in SCD prevention.
AIM: Chronic heart failure (CHF), caused by ischemic cardiomyopathy (ICM) and nonischemic cardiomyopathy (NICM), is among the leading causes of mortality and morbidity worldwide. Low-density lipoprotein receptor-related protein 6 (LRP6) plays a critical role in regulating Wnt signaling. Dysregulated Wnt signaling contributes to high incidence of arrhythmias. Thus, there might be an association between genetic variations of LRP6 and sudden cardiac death (SCD). The objective of the study was to examine the association between common variants of LRP6 METHODS: From July 2005 to December 2009, patients with CHF referred from 10 hospitals and participants without structural heart disease in China were undergone a prospective study. The single-nucleotide polymorphism rs2302684 was selected to evaluate the effect of LRP6 polymorphisms on the survival of the patients. RESULTS: A total of 1 887 patients (1 437 with CHF and 450 in the control group) were finally enrolled During the median follow-up of 61 months, a total of 546 (38.00%) patients died, including 201 (36.81%) cases with SCD and 345 (63.19%) cases with NSCD. No end point event occurred in the control group. Patients carrying A allele of rs2302684 had increased risks of allcause death (P <0.01) and SCD (P <0.01). After adjusted for the other risk factors, the association remained Significant in allcause death (P <0.01) and SCD (P <0.01). In patients with CHF caused by ICM, those carrying A allele of rs2302684 also had increased risks of all-cause death (P <0.01 ), and SCD (P <0.01). After adjusted for the other risk factors, the associations remained significant in all-cause death (P <0.01) and SCD association between A allele of rs2302684 and prognosis in patients with CHF caused by NICM. CONCLUSION: The SNP rs2302684 T> A in LRP6 is associated with an increased risk of all-cause death and SCD in patients with CHF in Chinese Han population, and the association is more prevalent in patients with CHF caused by ICM. Thus, LRP6 might be added as a novel predictor of SCD and could provide an attractive and direct therapeutic target in SCD prevention.