Comments on ‘Association of FcϵRIβ polymorphisms with risk of asthma and allergic rhinitis: evidence based on 29 case–control studies’

Abstract Guo et al. (Bioscience Reports (2018) 38, BSR20180177) published a meta-analysis concerning the association between five single nucleotide polymorphisms (SNPs) in the high-affinity IgE receptor β chain (FcεRIβ) gene, namely E237G, -109 C/T, RsaI_in2, RsaI_ex7, and I181L, and risk of asthma and allergic rhinitis based on available 29 case–control studies. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of association of SNPs in FcεRIβ gene with allergic diseases risk. They found that FcεRIβ E237G (237G vs. 237E: OR = 1.28, 95% CI = 1.06–1.53) and −109 C/T (TT vs. CT+CC: OR = 1.58, 95% CI = 1.26–1.98) were risk factors for allergic diseases. Guo et al.’s findings are interesting, but we found that several issues should be clarified after carefully reading the paper. Here, we intended to comment on these data clarifications.

Dear editor, We researched the relevant studies about the association between the high-affinity IgE receptor β chain (FcεRIβ) polymorphisms and allergic diseases risk in Medline, Embase, Web of Science, Chinese National Knowledge Infrastructure, and Wanfang databases. No limit of start year and month was set, and the updated time was August 2019. The terms, search strategies, and inclusion/exclusion criteria were the same as reported by Guo et al. [1]. Comparing our retrieved studies with the ones in Table 1 of Guo et al.'s paper [1], it seems that some errors or mistakes should be corrected.
Second, several studies published by the same research group were included in Guo et al.'s report [1]. According to the inclusion and exclusion criteria, when more than two studies were reported by the same research group, only the paper with the largest sample size was included in the analysis. We think Cui et al.'s study [16], published in 2004, with 106 adult asthmatics and 106 controls, were incorporated into their another paper, published in 2003, with 216 (number including adults and children) cases and 198 controls [17]. Similarly, the study populations in Hua et al.'s papers [18,19] and the Chinese Han case/control populations in Ramphul et al.'s article [20], were recruited by the same research group, the two smaller sample-size studies should be excluded from the analysis [18,20].    Third, one study reported by Laprise et al. [21], with atopic/non-atopic contrast groups, not all the subjects in atopic group met with the diagnosis criteria of asthma, should be excluded from the analysis.
Considering the above-listed mistakes or errors in Guo et al.'s published paper, it seems that the findings and conclusions of Guo et al.'s study were not entirely reliable [1]. To overcome the limitations, we performed an updated meta-analysis to re-assess the associations of C-109T and E+237G polymorphisms in the FcεRIβ gene with allergic disease (asthma and allergic rhinitis) risk. The statistical analysis methods and software used in this comment were the same as reported by Guo et al., unless otherwise indicated [1].
Sensitivity analysis was performed by sequentially omitting each individual study in the order of publication year and the pooled ORs were estimated repeatedly, which was used to evaluate the stability of the results of present meta-analysis. The sensitivity analysis showed that the association of EG and GG genotypes with increased risk of allergic diseases maintained statistically significant when removing any each individual study ( Figure 5). Egger's regression test and Begg's rank correlation test were used to evaluate the small-study effects and potential publication bias in current meta-analysis. Both tests indicated that the significant association of G allele or EG+GG genotypes with elevated risk of allergic diseases might strongly influenced by small-study effect or publication bias ( Table 3). The Egger's funnel plots for the association between E237G polymorphism and allergic diseases risk also showed that the OR distributions for both G allele vs. E allele ( Figure 6A) and EG+GG vs.EE ( Figure 6B) were obviously asymmetrical.
There are some inherent limitations of meta-analysis which should be taken into consideration when using the results of this comment. First, there was high heterogeneity in this meta-analysis, especially in the case of association of E237G variant with allergic diseases risk. Although, subgroup analyses were performed on the basis of ethnicity, allergic disease category and HWE, heterogeneity among the included studies still be statistically significant in all subgroups. Second, publication bias tests indicated that the probable existence of publication bias, i.e. some unpublished negative results studies thus could not be included in this analyses might result in an over-estimated association of E237G with allergic disease risk.
In conclusion, the results of Guo et al.'s study [1] should be interpreted with caution. To make an asserted conclusion, well-designed studies with large number of homogeneous population are required. We do hope that this comment will be helpful to clarify the results presented by Guo et al. [1].