GENES ENCODING HEAT-RESISTANT OBSCURE PROTEINS WITH CHAPERONE-LIKE ACTIVITIES-BBLN AND SERF2-ARE ASSOCIATED WITH CORONARY ARTERY DISEASE RISK: A PILOT STUDY.

BACKGROUND

Coronary artery disease (CAD) is one of the main death causes around the world. Molecular chaperones (MCs) are heavily implicated in the pathogenesis of CAD. The role of recently discovered MCs called Hero-proteins in the CAD development is still unknown, hence we are set out to study the effect of genes encoding Hero proteins - BBLN and SERF2 - on the CAD risk.

METHODS

The research included 2164 unrelated Russians (836 patients with CAD and 1328 healthy controls). SERF2 SNP rs4644832 and C9orf16 SNP rs2900262 were genotyped using allele-specific probe-based PCR. Statistical analysis was done using PLINK v1.9.0-b.7.7 and R software. The analysis was carried out in the whole group and additionally in the groups stratified by sex and smoking status.

RESULTS

The T allele of rs2900262 BBLN is a risk allele for females (OR=1.74, 95%CI 1.07-2.82, P=0.02), and, in contrast, has a protective effect in males (OR=0.56, 95%CI 0.36-0.88, P=0.01). The G allele of rs4644832 SERF2 is a risk allele for smokers (OR=1.34, 95%CI 1.004-1.79, P=0.047). Furthermore, in females the G allele is associated with a higher thrombocyte count (p=0.04) and a higher extent of left coronary artery damage (p=0.04).

CONCLUSIONS

This study reveals the novel genetic association between rs2900262 BBLN, rs4644832 SERF2 and the risk CAD risk. It allows to suggest that both Hero-proteins are involved in the pathogenesis of CAD via regulation of proteostasis.