Aim:The aim of this study was to assess whether rs1333049 was associated with coronary heart disease (CHD) in Han Chinese. Methods: This case-control study was involved with 599 CHD patients and 591 non-CHD controls. Meanwhile, a comprehensive meta-analysis was also conducted to establish the contribution of rs1333049 to CHD. Results: Our results showed that rs1333049 increased the risk of CHD by 38% (OR = 1.38, 95% CI = 1.18-1.62). A breakdown analysis by gender further indicated that rs1333049 increased the risk of CHD in men by 29% (OR= 1.29, 95% CI=1.05-1.58) and in women by 64% (OR= 1.64, 95% CI=1.25-2.16). A follow-up subgroup analysis by age showed there was a significant association between rs1333049 and CHD in women younger than 65 (≤ 55 years: p = 0.001, 55-65 years: p= 0.008) and in men aged between 55 and 65 years (p = 0.005). Our meta-analysis was involved with 21 studies (25 stages) among 20969 cases and 34114 controls. Our results showed that rs1333049 led to a significantly increased risk of CHD (OR = 1.30, 95% CI = 1.21-1.39). Further subgroup analyses by ethnicity showed rs1333049 increased the CHD risk by 30% in Europeans (OR = 1.30, 95% CI= 1.16-1.47) and 27% in Asians (OR=1.27, 95% CI=1.22-1.33). Conclusions: Our case-control study and meta-analysis suggest that rs1333049 is a useful risk marker of CHD.

Long QT (LQT) type 2 (LQT2) is caused by HERG mutation. L539fs/47 encodes a truncated protein, and its mechanisms in HERG mutation are unknown. HERG mutation plasmids were overexpressed in HEK293T cells, respectively, followed by analyzing lysates with Western blot. Transfected HEK293T cells were treated with or without N-acetyl-l-leucyl-l-leucyl-l-norleucinal (ALLN) and Propranolol (Prop) at 24 or 48 h. HERG-WT, HERG-A561V, WT/A561V, HERG-L539fs/47, WT/L539fs/47, and Calnexin (CNX)/Calreticulin (CRT) protein expression and their interactions were detected by Western blot and immunoprecipitation. Each group with HERG currents (Ikr) were detected by Patch-clamp technique. Treated with ALLN, the expression of mature HERG protein and the CNX/CRT protein increased. The interaction of HERG-A561V and WT/A561V protein with the chaperone CNX/CRT increased significantly. The maximum peak currents and tail currents density increased by 70% and 73%, respectively, while maximal peak currents density (24%) and tail currents density (19%) were slight increased in WT-HERG cells. Treated with Prop, the expression and interaction of mature HERG and chaperones CNX/CRT had no difference in each group. The maximal currents and tail currents density were slight increased. CNX/CRT might play a crucial role in the trafficking-deficient process and degradation of HERG-A561V mutant protein, however they had no effect on L539fs/47 HERG due to protein transport deletion. ALLN can restore HERG-A561V mutant protein trafficking process and rescue the dominant negative suppression of WT-HERG.

Coronary artery disease (CAD) has become the main cause of mortality worldwide. Lectin galactoside-binding soluble-2 () is involved in the cytokine lymphotoxin-α (LTA) cascade that may influence the progress of CAD. The aim of the present study was to assess the association between the 3279C>T (rs7291467) polymorphism and CAD. A total of 562 cases and 572 controls were recruited to examine the association. A systematic meta-analysis was performed to evaluate the contribution of 3279C>T polymorphism to the risk of CAD among 12,093 cases and 11,020 controls. There was no significant association found in the present case-control study. However, the meta-analysis showed that 3279C>T played a protective role in CAD [P=0.008, odds ratio (OR), 0.90; 95% confidence interval (95% CI), 0.82-0.97] and particularly in the Asian population (P=0.006; OR, 0.82; 95% CI, 0.71-0.94). The present case-control study did not find a significant association between 3279C>T and CAD in the Eastern Han Chinese population. However, the meta-analysis indicated that 3279C>T played a protective role in CAD, suggesting an ethnic difference in the association of the locus with CAD.