Genetic Variability of <i>IRF6</i> Polymorphisms in Non-Syndromic Cleft Lip/Palate: A Meta-Analysis Across Diverse Populations

<i>Background</i>Common congenital malformations known as orofacial clefts include cleft lip, cleft lip and palate, and cleft palate. They present significant public health challenges globally due to their medical, psychological, and socioeconomic impacts. Genetic and environmental factors mostly influence the genesis of nonsyndromic cleft lip with or without cleft palate.<i>Methods</i>A meta-analysis was carried out to evaluate the association between <i>IRF6</i> polymorphisms (rs2235371, rs2235373, and rs2235375) and NSCL/P. PubMed, Google Scholar, Scopus, and Embase were systematically searched for relevant articles. Studies meeting predefined inclusion criteria included case-control designs, genotype data, and statistical measures (odds ratios, 95% confidence intervals). Seventeen research papers were chosen based on the Newcastle-Ottawa Scale criteria for worth evaluation.<i>Results</i>The meta-analysis included 1809 NSCL/P cases and 3164 controls from diverse populations, including Chinese Han, Brazilian, South Indian, Northeast Chinese, Uyghur, Indonesian, Vietnamese, Mesoamerican, and Iranian groups. However, in our analysis, only specific <i>IRF6</i> SNPs-rs2235371 and rs2235373-showed significant associations in the allelic and dominant models, respectively, while other SNPs, including rs2235375, showed no significant association. These findings underscore the genetic heterogeneity of NSCL/P across various ethnic groups.<i>Conclusion</i>This meta-analysis emphasizes the complex role of <i>IRF6</i> polymorphisms in the genetic susceptibility to NSCL/P. While significant associations were identified in several populations, the lack of association in others suggests that genetic factors contributing to NSCL/P vary widely. Further research is needed to elucidate additional genetic determinants and their interfaces with environmental factors in the pathogenesis of NSCL/P.