Meta-analyses can assist in determining statistical significance across studies that appear to have contradictory results. The statistical significance established when multiple researches are considered at once is significantly higher than when one study is considered alone [21]. Some of the benefits of meta-analysis include a pooled estimate of impact, an objective assessment of evidence, and the ability to explain heterogeneity between research results [22].
This meta-analysis found three HLA-DRB1 alleles (*01, *04, and *10) which have been shown to be predisposing for RA. The controls, on the other hand, are favored by four HLA-DRB1 alleles (*03, *07, *11, *13, and *14) which were shown to be significantly lower in RA patients than in controls allele group, potentially decreasing the risk of disease development. However, no association was observed across five HLADRB1 alleles (*08, *09, *12, *15, and *16).
Despite the fact that there is no significant link (P = 0.006), the forest plot HLA-DRB1*01 has showed that is more likely to develop RA than controls. This may be because of the longer confidence interval on individual studies. Closer to our findings, two studies from Syria (OR = 2.29, 95%CI = 1.11–4.75, P = 0.022) [14] and Turkey (OR = 1.99, 95%CI = 1.19–3.33, P = 0.04) [6] both found a robust link of RA in the allele group. HLA-DRB1*01 has also been linked to the risk of RA in areas of northeastern Spain [23] and India [24].
Our findings on the DRB1*0401 genotype group demonstrate a predisposition to RA, which is consistent with research in European populations [16] that reveal DRB1*0401 is one of the most important genetic risk factors for RA. Also the prevalence of DRB1*0401 is significantly higher in RA patients, according to a report in the Chinese population [25]. In contrast to research DRB104:05 is negatively related with RA in Japanese people [20], however our pooled findings reveal no connection at all with this subgroup across included studies.
Interestingly, unlike many other research, HLA-DRB1*14 was found to be protective in our pooled effects. There are research that do not complement our findings of alleles include: The HLA-DRB1*14 (OR = 2.74) allele and RA are linked in a study of a mixed Peruvian population (n = 65) [26]. Similarly, according to another research the HLA-DRB1*14 allele has demonstrated a tendency to be associated with RA was observed in Yakima Indians, a Native American tribe[27].
The HLA-DRB1*09 alleles, which are found to be a predisposing factor on RA patients of Malaysia [28], are not observed in our study. No correlation was found in our study (OR = 1.42, 95%CI = 0.68–2.96, p = 0.34). This difference could be due to the fact that these studies had a larger sample size, resulting in statistical significance in this association.
HLA-DRB1*04 was found to be predisposing against RA in our study, as well as in studies of RA patients from Portuguese [29], Spain [30], and United Kingdom [31]. There are, of course, some multiple theories about this allele. For instance, some study revealed a significant rise in the frequency of HLA-DRB1*04 alleles in RA patients [32], whereas, others found no such associations [25]. Curiously, like many other research, HLA-DRB1*04 was found to be positive association with RA in our pooled effects. But HLA-DRB1*01 and HLA-DRB1*04 alleles appear to be linked to a decreased chance of developing RA [33, 34], which is not consistent with our findings.
Differences in ethnic groupings, geographic region, and HLA genotype might explain the contradictory results. Differences in ethnic groupings, geographic location, HLA genotyping methods, and sample size may be to blame for the mixed results. Because of the high shared epitope (SE) in the area, it would be best to examine at all genotype level in future study.
The lack of a link between HLADRB1*04 and RA in Greek patients was confirmed in one study. In general, our findings provide a tremendous insight into HLA-DRB1 and the risk of having RA, which are both consistent with and contradictory to the findings of many research around the world. This could be because our analysis did not include a European group by default, or because the majority of these studies focus on early disease start.
However, this meta-analysis has certain limitations. We do not take European HLA-DRB1 into account by chance, which is something that other researchers may do in the future. Since ethnicity and geographical differences are important variables in gene-association research.