Association between post–surgery wound healing and endothelial nitric oxide synthase genetic polymorphisms in patients with cleft palate disorder

Cleft palate is a congenital craniofacial malformation that is usually diagnosed in the neonatal or infantile period. In a study conducted at Hacettepe University Faculty of Medicine for the Turkish population, it was determined that out of 1229 patients treated, 45% had both cleft lip and palate, and 35.6% had isolated cleft palate. The only treatment for cleft palate and/or cleft lip anomalies is surgery and palatoplasty is applied. It is recommended that palatoplasty should ideally be performed between 6 and 9 months and this period should not exceed 18 months. After surgery, bilateral wounds in the areas where the relevant segments of the palate are removed and left to heal. The wound left to close heals in up to four weeks in clinical practice, and this time varies among patients. Endothelial nitric oxide synthase (eNOS) is one main enzyme responsible for constitutive nitric oxide production. NO ensures the continuity of blood flow to the organs through the vascular endothelium and through angiogenesis. In a study conducted on Nos3 knock-out mice, it was shown that wound closure time was prolonged, and new vessel formation was significantly delayed as compared to Nos3 wild-type mice. The aim of this study was to investigate the effects of T(-786)C (rs2070744), 4b/a (27bp-VNTR), and G894T (Glu298Asp, rs1799983) polymorphisms of the NOS3 gene on wound healing after palatoplasty in the Turkish population. Patients (n=112) with cleft palate anomaly were included in the study. 91 patients whose wound closure occurred in a "normal" time (between 1-4 weeks) were evaluated as Group I, and 21 patients with delayed wound closure (>4 weeks) were considered as Group II. Genotyping was performed using polymerase chain reaction (PCR) and restriction analysis. There were significant differences in the distribution of genotype and allele frequencies for NOS3 T(-786)C and 27-bp VNTR 4b/a genetic polymorphisms between Group I and Group II, while the distribution of those for NOS3 G894T genetic polymorphism was similar between the groups. Our results suggest that eNOS (NOS3) genetic polymorphisms may be useful as markers in monitoring the wound healing process after palatoplasty and that eNOS might be a possible drug target if the resuts would be supported by further research.