Preliminary Analysis of the Nonsynonymous Polymorphism rs17563 in BMP4 Gene in Brazilian Population Suggests Protection for Nonsyndromic Cleft Lip and Palate

Abstract EN

Cleft lip with or without palate (CL±P) is common congenital anomalies in humans.

Experimental evidence has demonstrated that bone morphogenetic protein 4 gene (Bmp4) is involved in the etiology of CL±P in animal models.

The nonsynonymous polymorphism rs17563 T>C (p.V152A) in the BMP4 gene has been associated to the risk of nonsyndromic CL±P in Chinese population and microforms from different ethnic backgrounds.

The aim of this study was to investigate the role of BMP4 gene in CL±P in Brazilian sample using genetic association approach.

Our sample was composed by 123 patients with nonsyndromic CL±P and 246 controls, in which absence of CL±P was confirmed in 3 generations.

The rs17563 polymorphism was genotyped by PCR-RFLP technique.

Logistic regression was performed to evaluate allele and genotype association.

Our data showed statistical power to detect association (86.83%) in this sample.

Logistic regression results showed significant association between C allele and CL±P (P=0.00018, OR =0.40, and 95% CI = 0.25–0.65), as well as CC genotype and CL±P (P=0.00018, OR =0.35, and 95% CI = 0.19–0.66).

So, there is a strong association between nonsyndromic CL±P and BMP4 rs17563 polymorphism in our sample and the C allele had a protective effect against the occurrence of nonsyndromic CL±P.