IL6R haplotype rs4845625∗T/rs4537545∗C is a risk factor for simultaneously high CRP, LDL and ApoB levels

Abstract

Interleukin 6 receptor (IL-6R), mediating IL-6's biological functions, plays an important role in different diseases such as diabetes, obesity and cardio-vascular diseases. In this study, we investigated the effects of two single nucleotide polymorphisms (SNPs), within the IL-6R loci, previously associated with C-reactive protein (CRP) and coronary heart diseases risk, and with controversial effects on lipids traits: SNP rs4845625 and SNP rs4537545. The results showed that both investigated SNPs were antagonistically related with CRP levels; the minor rs4845625∗T allele was associated with increased CRP levels (P-value=0.011), while the minor rs4537545∗T allele was associated with decreased CRP levels (P-value=0.009). Interestingly, the minor rs4845625∗T allele was significantly associated with higher low-density lipoprotein cholesterol (LDL-C) and ApoB levels (P=0.007 and P=0.009 respectively). Haplotype analysis showed that the TC haplotype, having the minor rs4845625∗T allele, was related simultaneously with increased levels of CRP, LDL-C and ApoB levels, thus could be considered as a risk factor. Our investigation detects for the first time an independent effect of rs4845625 on LDL-C and ApoB traits, explaining an important range of those traits variability (3.49 and 5.57% respectively). Our findings might be of high clinical significance in pharmacogenomics studies of tocilizumab for which IL-6R is target.