Association Between IRF6 Variants and Nonsyndromic Cleft Lip With or Without Cleft Palate in Chile
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ORIGINAL ARTICLE
Association Between IRF6 Variants and Nonsyndromic Cleft Lip With or Without Cleft Palate in Chile José Suazo 1 & Andrea S. Recabarren 1 & Nicolás R. Marín 1 & Rafael Blanco 2 Received: 15 January 2020 / Accepted: 2 April 2020 # Society for Reproductive Investigation 2020
Abstract The aim of this study was to assess the association between IRF6 single nucleotide polymorphisms and nonsyndromic cleft lip, with or without cleft palate (NSCL/P), in a Chilean population, based on a case-control sample and confirmed in a case-parent trio population. In a sample of 150 Chilean case-parent trios and 164 controls (cohort 1), we evaluated the association between three common IRF6 variants (rs764093, rs2236909, rs2235375) and NSCL/P using odds ratio (OR) for case-control and case-parent trios and in a combined OR of both designs. To confirm associations from the cohort 1, we increased the sample size to 215 triads and 320 controls (cohort 1 + cohort 2). The combined OR for the cohort 1 reveals that the rs2235375 C allele is associated with NSCL/P in Chile (OR 1.34; p = 0.013), which was supported by the results for the two cohorts (OR 1.29; p = 0.006). Bioinformatic prediction showed that this variant, located 27 bp downstream from IRF6 exon 6, potentially alters the splicing process and based on functional annotations is associated with a decrease of gene expression. We propose that the C allele of rs2235375 from IRF6 gene seems to be a risk factor for NSCL/P in a Chilean population. However, we cannot discard a population stratification bias in our findings. On the other hand, further studies are necessary to confirm the biological role of rs2235375 in IRF6 function at craniofacial development level. Keywords Nonsyndromic cleft lip with or without cleft palate . IRF6 . Case-control . Case-parent trios
Introduction The most prevalent birth defects affecting the craniofacial territory are orofacial clefts (OFCs) [1]. These defects include embryological anomalies in the closure of both the upper lip (cleft lip of CL) and palate (cleft palate or CP), where CL can be accompanied, or not, by a CP, which is classified as CL with or without CP (CL/P) [2]. In Chile, the prevalence of CL/ P and CP reaches 2.1 occurrences/1000 newborns. This rate Electronic supplementary material The online version of this article (https://doi.org/10.1007/s43032-020-00203-9) contains supplementary material, which is available to authorized users. * José Suazo [email protected] 1
Instituto de Investigación en Ciencias Odontológicas, Facultad de Odontología, Universidad de Chile, Sergio Livingstone # 943, Santiago, Chile
2
Programa de Genética Humana, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile
makes OFC the second most prevalent birth defect in our country [3]. OFCs have become a major public health problem in Chile, and worldwide, due to its prevalence, its associated medical complications, and the cost and time of rehabilitation [4, 5]. Around 70% of subjects affecte
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