ULK1 polymorphisms confer susceptibility to pulmonary tuberculosis in a Chinese population.

Abstract

The autophagy pathway is a critical process in Mycobacterium tuberculosis infection, and can be regulated by uncoordinated 51-like kinase 1 (ULK1). We investigated the associations between single-nucleotide polymorphisms (SNPs) in ULK1 and risk of tuberculosis (TB) in a Chinese Han population. We recruited 380 pulmonary tuberculosis (PTB) cases, 242 extra-pulmonary tuberculosis (EPTB) cases and 606 healthy controls from a Chinese Han population and sequenced ULK1. Five SNPs in ULK1 were selected to investigate the correlations between ULK1 polymorphisms and TB susceptibility. The rs7138581 C allele was associated with a reduced risk of PTB (P = 0.001), whereas the rs9481 A allele was associated with an increased risk (P = 0.025). The rs7138581 CG genotype was significantly associated with a low risk of PTB, with a higher PTB disease severity in clinical parameters. Estimation of haplotype frequencies in ULK1 revealed a protective haplotype CCGAA (P = 0.007) and a potential risk haplotype TGAAA (P = 0.010) for PTB. These results demonstrated that ULK1 polymorphisms have significant associations with susceptibility to PTB.