Preliminary Analysis of the Nonsynonymous Polymorphism rs17563 in BMP4 Gene in Brazilian Population Suggests Protection for Nonsyndromic Cleft Lip and Palate
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 ( , OR , and 95% CI = 0.25–0.65), as well as CC genotype and CL±P ( , OR , 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. 1. Introduction Nonsyndromic cleft lip with or without palate (CL P) is a congenital defect with multifatorial transmission. It is a birth defect that occurs with a prevalence of 1 in 500 to 1 in 2500 live births in different populations, varying with geographic location, ethnic group, and socioeconomic conditions [1–3]. Populations of either American native descent or Asian descent have the highest birth prevalence [4]. In Latin America, according to the ECLAMC (Latin American Collaborative Study of Congenital Malformations), the incidence of this malformation is 1 in 850 births [5]. CL P has a complex etiology that includes strong genetic and environmental factors. Clinically, CL P are classified as nonsyndromic (isolated) or syndromic based on the presence of other congenital anomalies or mental disabilities [1, 6]. Around 400 recognizable syndromes that have CL P as part of the phenotype are described [7, 8], however, 70% of CL P cases are nonsyndromic. Approximately 12–25% of the genetic variations associated with nonsyndromic CL P have been identified [1, 6]. Although genetic studies have identified a number of candidate genes and chromosomal regions associated with CL P, findings from different studies have been inconsistent [9, 10]. Candidate genes for CL P have been proposed as result of
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