Association of Genetic Polymorphisms of GREM1 Gene with Susceptibility to Non-Syndromic Cleft Lip with or without Cleft Palate in an Iranian Population

Background: Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is common congenital birth anomaly with multifactorial etiology. The GREM1 gene has been proposed to play a role in oral clefts development. Objective: The aim of the present study was to evaluate the correlation between GREM1 polymorphisms and the risk of NSCL/P in an Iranian population. Methods: Genotyping of rs7162202, rs12915554, rs3743105, rs1129456, and rs10318 polymorphisms of GREM1 gene in 150 NSCL/P and 152 healthy subjects was determined by the PCR-RFLP or T-ARMS-PCR. Results: The findings showed that the rs12915554 variant significantly increased the risk of NSCL/P in heterozygous (OR = 4.20, 95%CI = 2.46-7.11, p < 0.0001, AC vs AA), and allele (OR = 3.17, 95%CI = 2.00-5.08, p < 0.0001, C vs A) genetic models. The rs3743105 polymorphism was correlated with reduced risk of NSCL/P in heterozygous (OR = 0.49, 95%CI = 0.29-0.83, p = 0.008, AG vs GG) and dominant (OR = 0.54, 95%CI = 0.33-0.89, p = 0.018, GA + AA vs GG) genetic models. The rs1129456 variant was positively associated with the risk of NSCL/P in heterozygous (OR = 2.91, 95%CI = 1.12-7.38, p = 0.028, AT vs AA) and allele (OR = 2.80, 95%CI = 2.80-6.95, p = 0.031, T vs C). The rs10318 polymorphism significantly reduced NSCL/P risk in homozygous (OR = 0.20, 95%CI = 0.06-0.67, p = 0.013, TT vs CC), dominant (OR = 0.57, 95%CI = 0.36-0.91, p = 0.019, CT + CC vs CC), recessive (OR = 0.24, 95%CI = 0.07-0.76, p = 0.031, TT vs CT + CC), and allele (OR = 0.57, 95%CI = 0.38-0.84, p = 0.005, T vs C). No correlation was observed between rs7162202 polymorphism and NSCL/P. Conclusion: The findings support that GREM1 polymorphisms are involved in NSCL/P susceptibility in an Iranian population.