Association of ATG12 EQTL With HNSCC Risk in Chinese Population

Objectives: To evaluate whether the genetic variants in autophagy-related genes influence the head and neck squamous cell carcinoma (HNSCC) risk among Chinese population
Methods: We conducted a case-control study to analyze 11 tagging single nucleotide polymorphisms (SNPs) in core autophagosome formation genes with 576 HNSCC cases and 1552 healthy controls.
Results: We identified that rs26537 of ATG12 and rs4663402 in ATG16L1 were significantly associated with the increased risk of HNSCC. The results of expression quantitative trait loci (eQTL) analysis based on Genotype-Tissue Expression (GTEx) accessible data, showed that the risk alleles of rs26537 were significantly associated with up-regulated expression of ATG12 in whole blood (P < 0.001). Further luciferase activity assay indicated that rs26537 T>C in ATG12 intron 1 region significantly enhanced transcription activity.
Conclusions: These results suggested that ATG12 eQTL SNP rs26537 influenced the enhancer activity, contributing to an allele-specific effect on the expression of host gene ATG12, which might explain a fraction of HNSCC genetic susceptibility.