The Suggestive Association Between the <i>NOG</i> rs227731 Polymorphism and Non‐Syndromic Cleft Lip With or Without Palate Subtypes in a Japanese Cohort

Non-syndromic cleft lip with or without palate (NSCL/P) ranks among the most prevalent congenital craniofacial anomalies globally. In Japan, reported rates of cleft lip and/or palate range from 1 in 500 to 1 in 700 live births. This study aims to explore potential sex-specific interactions of NOG rs227731 across NSCL/P subtypes in a Japanese population. This case-control study included 420 participants recruited from the Cleft Lip and Palate Centre at Aichi Gakuin Dental Hospital in Nagoya, Japan. The study population was divided into three groups: 110 individuals with non-syndromic cleft lip and palate (NSCLP), 110 with non-syndromic cleft lip only (NSCLO), and a control group of 200 unaffected individuals. A balanced 1:1 male-to-female ratio was maintained within each group to enhance the statistical power of sex-stratified analyses. There was no evidence about the association of rs227731 with NSCL/P and the NSCLP group in both gender clusters. In the NSCLO subgroup, a significant difference emerged in the allelic model among males (OR = 1.66, 95% CI: 1.03-2.69, p = 0.0385). Conversely, no significant associations were detected in females across any of the models. In conclusion, this study's findings suggest a possible association between the NOG rs227731 variant in males of NSCLO as an increasing risk factor.