T cells play an important role in β-lactam allergy. They are reported to be involved in various types of hypersensitivity (Kim et al., 2005; Rubio et al., 2010). T helper (Th) 1 and Th2 cells are the two types of T cells. Th2 cells can be involved in immunoglobulin E (IgE)-mediated immediate hypersensitivity as they promote the secretion of cytokines such as IL-4, IL-5, IL-6, IL-10, and IL-13 (Palomares, 2013).
IL-10 can inhibit the clonal expansion of Th0, Thl, and Th2 cells (Jiang, 2015), and it plays an important role in the occurrence and development of allergy. This study selected rs1800871, rs1800872, and rs1800896, which directly affected the expression of IL-10. Apter et al. (2008) reported that there was no significant correlation between IL-10 genetic polymorphism and β-lactam allergy. Guglielmi et al. (2006) suggested that IL-10 promoter and IL-4Rα genetic polymorphisms were related to immediate β-lactam allergy in female patients. The results of present study show that rs1800872 of IL-10 was not correlated with β-lactam allergy in the Han Chinese population of Northwest China. Additionally, three types of haplotype, CCA, CCG, and TAA of IL-10, were not found to be correlated with β-lactam allergy in the Han Chinese population. The study data were consistent with the findings of Apter et al. (2008); however, it was not consistent with that of Guglielmi et al. (2006). The reason might be that because our SNP chip is based on Sequenom MassARRAY® technology which is used to perform high-throughput sequencing. The chip presented high sensitivity and specificity, so the results are more reliable. The researchers have utilized different technologies including classic sequencing and high-sensitive PCR. The threshold for the detection of gene expression might be further explored using such procedures. Guglielmi et al. (2006) and Apter et al. (2008) have proved that other important factors, such as race, region, and environmental conditions, can also influence the distribution of genotype.
The IL-4Rα gene was located on chromosome 16p11–16p12. It is a subunit that plays a key role in allergic disease by promoting the IgE production (Wu and Scheerens, 2014). The present study showed that the distribution frequency of rs1801275 of IL-4Rα was not significantly different between the groups (P>0.05), and the same results were obtained when the patients were stratified by gender (P>0.05).
IL-13 was mainly involved in the allergic reactions through inducing the B lymphocytes to secrete IgE antibodies (Ford et al., 2001). IL-13 and IL-4 were isogenous, because of their chromosomal localization and the molecular composition of proteins. Additionally, the sharing receptor structure presented the same signal pathway, and it also demonstrated similar physiological functions. IL-13 can indirectly play a role in eosinophils by upregulating the expression of eotaxin, and the effect of IL-13 was greater than that of IL-4 (Levine and Wenzel, 2010). The present study results showed that the distribution frequencies of three SNPs of IL-13 gene such as rs20541, rs1881457, and rs1800925 were not significantly different between the case and control groups (P>0.05). The same results were obtained when the patients were stratified by gender (P>0.05). Six haplotypes were constructed on these three SNPs of IL-13 gene, in which CCT was only one observed in the control group (F=0.026) but not in the case group. The F-value of CAC was 0.069. Therefore, the relationship between these two haplotypes and β-lactam allergy in the Han Chinese population of Northwest China requires further study.
The study of SNPs of FcεRIβ and IFNGR2 mainly focused on their relationships with allergic diseases such as asthma (Kim and Park, 2006; Sanak et al., 2007) and allergic rhinitis (Nagata et al., 2001), and was used to treat malignant tumors such as non-Hodgkin lymphoma (Purdue et al., 2007; Chen et al., 2011) and gastric cancer (Hou et al., 2007). IFNGR1 was reported to correlate with β-lactam allergy, however, the relationship between SNP of IFNGR2 and β-lactam allergy was not clear. The study showed that the SNPs of both FcεRIβ and IFNGR2 were not correlated with β-lactam allergy.
Cytochrome P450 is widely distributed across all living organisms including vertebrates, invertebrates, plants, fungi, and bacteria. It was one of the most widely distributed enzymes of phase I drug metabolism, and it presented the richest natural content and the broadest substrate spectrum. Furthermore, CYP is distributed in various organs and tissues of the human body. CYP3A subfamily was one of the major rate-limiting enzymes in drug metabolism (Gellner et al., 2001). Four genotypes were involved in drug metabolism in humans including CYP3A4, CYP3A5, CYP3A7, and CYP3A43 (Gibson et al., 2002).
The correlation between the SNPs of CYP3A4 and β-lactam allergy was not reported in the past, and we found that the rs2242480 of CYP3A4 gene was correlated to β-lactam allergy in male patients. The frequency of genotype CT was significantly different between the case and control groups when compared with the wild-type gene CC (P=0.022; OR=0.167, 95% CI: 0.032–0.867).
