Carnitine palmitoyl transferase 2 polymorphism may be associated with enterovirus 71 severe infection in a Chinese population

Abstract

Genetic polymorphism in the carnitine palmitoyl transferase 2 (CPT2) gene has been reported to be a susceptibility factor in a number of syndromes of acute encephalopathy with various infectious diseases, but evidence of its effect on enterovirus 71 (EV71) infection is lacking. The goal of this study was to examine the relationship between genetic polymorphism of CPT2 and severity of EV71 infection in a Chinese population. PCR of five exons of the CPT2 gene was carried out to identify single-nucleotide polymorphisms (SNPs) in EV71-infected subjects (n = 333), including mild cases (n = 271) and severe cases (n = 62) as well as healthy controls (n = 328). Blood ATP levels were measured within 24 h of admission. The frequency of the A allele of rs1799821 (P = 0.023) and the G allele of rs2229291 (P = 0.009) in the CPT2 gene was higher in patients with severe EV71 infection. The A-G haplotype of rs1799821and rs2229291 was directly linked to EV71 severe infection risk when compared to all other haplotypes (OR = 2.005, 95 % CI = 1.087-3.700, P = 0.024). The blood ATP levels of severe cases were significantly lower than in mild cases (P < 0.01) and controls (P < 0.01). A significant negative correlation was observed in haplotype A-G between ATP levels and physical findings in severe cases (P < 0.05). These findings suggest that CPT2 polymorphism may be associated with severity of EV71 infection and that the A-G haplotype of the CPT2 gene is involved in the inflammatory process of EV71 infection.

Association of the IRAK4 rs4251545 genetic polymorphism with severity of enterovirus‐71 infection in Chinese children

“…Some polymorphisms of EV71 receptors (such as TLR3 and TLR4) have been shown to be involved in the inflammatory pathogenesis of EV71 infection 6,17 . Genetic polymorphisms of some inflammatory mediators (such as OAS3, IL‐4 , and CPT2 ) have also been shown to be associated with susceptibility to EV71 infection 5,18–21 . Evidence that host genetic polymorphisms affect the susceptibility and severity of EV71 infection is increasing.…”

“… 6 , 17 Genetic polymorphisms of some inflammatory mediators (such as OAS3, IL‐4 , and CPT2 ) have also been shown to be associated with susceptibility to EV71 infection. 5 , 18 , 19 , 20 , 21 Evidence that host genetic polymorphisms affect the susceptibility and severity of EV71 infection is increasing. IRAK4 is indispensable for responses to IL‐1 and ligands that stimulate various TLRs; therefore, it plays a significant role in mediating the innate immune response induced by EV71.…”

Association of Interleukin-17F gene polymorphisms with susceptibility to severe enterovirus 71 infection in Chinese children

“…In recent years, many association studies between host genetic factors and EV71 infection have been performed. Our lab has previously demonstrated that polymorphisms in genes of IL-8, IL-10, IFN-γ, IL-6, IL-4, CXCL-10, CCL-2, TLR3, OAS3 and CPTII were associated with the susceptibility and/ or the severity of EV71 infection [24][25][26][27][28][29][30][31][32]. These cytokines/ chemokines and receptors are all necessary for an efficient inflammatory response.…”

TMEM173 rs7447927 genetic polymorphism and susceptibility to severe enterovirus 71 infection in Chinese children

“…Recent studies have mainly focused on exploring the relationship between EV71 infection and host immunity at the molecular level, and it has been found that human gene polymorphisms, such as those of CPT2, OAS2, and IL-17F, are related to infection susceptibility and severity. [5][6][7][8][9] The transmembrane protein 173 (TMEM173), also known as MPYS, mediates the interferon regulatory factor 3 (IRF3) activation (MITA), endoplasmic reticulum interferon stimulator (ERIS), stimulator of interferon genes (STING), and stimulator of interferon response cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) interactor 1 (STING1). Human TMEM173 is located on chromosome 5q31.2, contains eight exons, and encodes a transmembrane protein between the endoplasmic reticulum and Golgi in response to the presence of cytosolic dsDNA as well as an adaptor protein that mediates the production of type I interferon.…”