IRF6 Gene Polymorphisms Influence the Susceptibility of Nonsyndromic Cleft Lips With or Without Palate: A MOOSE-Compliant Meta-Analysis.
Rubin Sahu, Subhra Malinee Mishra, Prasad Nalabothu et al.
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In 30 seconds
This MOOSE-compliant meta-analysis pooled 53 published case-control studies to assess six IRF6 polymorphisms and susceptibility to nonsyndromic cleft lip with or without palate (CL ± P) across ethnic groups. Under the dominant model, rs642961 was associated with increased risk (AA + AG vs GG; OR: 1.31; 95% CI: 1.10-1.55; P < .02; I 2 = 70%), whereas rs2235371 was associated with reduced risk (AA + AG vs GG; OR: 0.74; 95% CI: 0.60-0.92; P < .007; I 2 = 75%). The other four polymorphisms showed no overall association; subgroup findings varied by ethnicity.
Key findings
- rs642961 was associated with increased CL ± P risk (AA + AG vs GG; OR: 1.31; 95% CI: 1.10-1.55; P < .02; I 2 = 70%).
- rs2235371 was associated with reduced CL ± P risk (AA + AG vs GG; OR: 0.74; 95% CI: 0.60-0.92; P < .007; I 2 = 75%).
- rs861019, rs2013162, rs2235373, and rs2235375 were not associated with overall CL ± P risk.
- Ethnicity subgroup analyses found rs861019 associated with increased risk in Caucasians, rs642961 with increased risk in Asians and mixed populations, and rs2235371 with reduced risk only in Caucasians.
Why it matters
The findings support an association between selected IRF6 variants and CL ± P susceptibility, while indicating that associations may differ across ethnic groups. This is relevant to interpreting genetic risk evidence: pooled estimates may not apply uniformly across populations, and the reported heterogeneity for the two overall associations underscores the need for cautious interpretation.
What to keep in mind
The pooled estimates showed substantial heterogeneity for rs642961 and rs2235371 (I 2 = 70% and I 2 = 75%, respectively). The authors also note that further studies in diverse cohorts are needed to validate population-specific findings.