Expression quantitative trait loci in long non-coding RNA ZNRD1-AS1 influence cervical cancer development

Am J Cancer Res. 2015 Jun 15;5(7):2301-7. eCollection 2015.

Abstract

Zinc ribbon domain containing 1 (ZNRD1) may play integral roles in immune response against HPV infection and cervical cancer. Its antisense transcript, ZNRD1-AS1, is an important regulator of ZNRD1. By bioinformatics analyses, we identified that several single nucleotide polymorphisms (SNPs) in ZNRD1-AS1 may be expression quantitative trait loci (eQTLs) for ZNRD1. So we hypothesized that these eQTLs SNPs in ZNRD1-AS1 may influence the susceptibility of cervical cancer through influencing ZNRD1 expression. We designed a population-based case-control study containing 1486 cervical cancer patients and 1536 controls to test the associations of three ZNRD1 eQTLs SNPs (rs3757328, rs6940552 and rs9261204) in ZNRD1-AS1 with the risk of cervical cancer. Logistic regression analyses in additive genetic model showed that all the three eQTLs SNPs decreased the risk of cervical cancer. Compared with those carrying "0" variant allele, subjects carrying "1-6" variant alleles had a 20% decreased risk of cervical cancer. Moreover, the haplotype containing variant alleles of these three SNPs significantly decreased the risk of cervical cancer when compared with the most frequent haplotype. In conclusion, ZNRD1 eQTLs SNPs in ZNRD1-AS1 could have a predisposition for the development of cervical cancer.

Keywords: ZNRD1; ZNRD1-AS1; cervical cancer; eQTLs.