AKT1 polymorphisms are associated with tuberculosis in the Chinese population

Abstract

AKT1, a serine/threonine kinase, plays a critical role in the controlling of intracellular growth of Mycobacterium tuberculosis. In this study, we investigated whether polymorphisms in AKT1 affect susceptibility to tuberculosis (TB). Two single nucleotide polymorphisms of AKT1, IVS3+18C>T and +726G>A were genotyped in Chinese patients with pulmonary TB by polymerase chain reaction-restriction fragment length polymorphism. Patients with pulmonary TB had significantly lower IVS3+18 C/C genotype and higher C/T genotype compared with age-, gender- and ethnically matched controls (P < 0.05). The T-A haplotype frequency was significantly higher in patients than in controls (P < 0.05). In conclusion, our result indicates that AKT1 polymorphisms are associated with susceptibility to pulmonary TB.

Polymorphism in cathelicidin gene (CAMP) that alters Hypoxia‐inducible factor (HIF‐1α::ARNT) binding is not associated with tuberculosis

“…One possible explanation for this could be due to the role of variation in genes that control the host immune response to the bacilli (Cobat et al ., ; El Baghdadi et al ., ). Genetic susceptibility to tuberculosis is influenced by host polymorphisms mainly in genes vitamin D receptor ( VDR ) (Alagarasu et al ., ), ubiquitin–protein ligase ( UBE3A ), IL12, surfactant pulmonary‐associated protein A1 ( SFTPA1 ) (Schurr, ), purinergic receptor P2X, ligand‐gated ion channel 7 (P2X7) (Li et al ., ), chemokine, CC motif, ligand 5 or RANTES ( CCL5 ) (Selvaraj et al ., ), V‐AKT murine thymoma viral oncogene homolog 1 ( AKT1 )(Wang et al ., ), solute carrier family 11, proton‐coupled divalent metal ion transporter ( SLC11A1 ) (Awomoyi et al ., ), interleukin‐12 receptor, beta‐1 ( 1L12RB1 ) (Kusuhara et al ., ), interferon‐gamma ( IFNG ) (Ding et al ., ), interleukin‐10 ( IL10 ) (Tso et al ., ), tumour necrosis factor alpha ( TNFA ) (Stein et al ., ) and Toll‐like receptor 4 ( TLR4 ) (Modlin, ).…”

Regulation of matrix metalloproteinase‐1, ‐3, and ‐9 inMycobacterium tuberculosis‐dependentrespiratory networks by the rapamycin‐sensitive PI3K/p70S6Kcascade

“…AKT is an important downstream kinase in the PI3K cascade (16) and AKT1 polymorphisms were associated with susceptibility to pulmonary TB (24). Mtb rapidly phosphorylates AKT in human macrophages, and its inhibition blocks Mtb-induced TNF-␣ generation (25).…”

Integrated Network Pharmacology Approach to Evaluate Bioactive Phytochemicals of Acalypha indica and Their Mechanistic Actions to Suppress Target Genes of Tuberculosis

“…AKT1 is a serine/threonine protein kinase that belongs to the Akt kinase family (Akt1, Akt2, and Akt3) . Mtb’s subcellular proliferation is controlled by the serine/threonine kinase AKT1 . In mice macrophages, the AKT1 inhibitor H-89 was reported to minimize pathogen growth and AKT1 and AKT2 knockdown in human THP-1 cells decreased the intracellular proliferation of pathogens. , AKT1 signaling can also influence the adaptive immune response, which includes T and B cells.…”