Association between rs642961 and cleft lip and palate in Patagonia (ECLAMC) population

CARVALHO FM, VIEIRA AR, POLETTA F, MEREB JC, FONSECA RF, LOPEZ CAMELO J, CASTILLA EE, ORIOLI IM

Montreal

Congreso; 12th International Congress of Human Genetics / 61st Annual Meeting of the American Society of Human Genetics; 2012

American Society of Human Genetics

Cleft lip with or without cleft palate (CL/P) birth prevalence is about 1/1,000 live births. In South America four CL/P high prevalence regions was detected, one of them being the Patagonia (Argentina). Significant association between the ancestral allele of the single nucleotide polymorphisms (SNPs) rs2235371(C>T) in the IRF6 gene and CL/P was inconsistently shown in multiple populations. Recently it was proposed that the ancestral allele of rs2235371(C>T) does not have an association with clefting independently of the mutated allele of the SNP rs642961(G>A) near the IRF6 region. We tested for association between these SNPs in IRF6 region (rs2235371C>T and rs642961G>A) and the risk of CL/P, using case-parent trio design in a high frequency CL/P population from Patagonia (Argentina). Five-hundred and twenty-six individuals from 129 families were selected through the Latin-American Collaborative Study of Congenital Malformations (ECLAMC). Genotyping was carried out by using TaqMan®SNP genotyping assays on the ABI Prism 7900HT. Haplotype and transmission distortion analyzes were performed with the Family Based Association Test (FBAT). We found an association between rs642961(G>A) around the IRF6 gene and CL/P with over transmission of the ancestral allele (f (G)=0.70, Z=2.042, p=0.04) in this population. This association remained when we analyzed a subgroup of 52 families (217 individuals) from El Bolsón and neighborhood villages (Lago Puelo, Ñorquincó, El Maitén, El Mallín Ahogado, Los Menucos, Maquinchao, Ingeniero Jacobacci) (f(G)=0.69, Z=2.616, p=0.009) and disappeared when we excluded this subgroup from the analysis (f(G)=0.71, Z=0.533, p=0.60), suggesting some kind of heterogeneity in this population. The variant rs2235371 is not associated with CL/P in this population. The association between the rs642961 (G>A) and CL/P, through the ancestral allele in some populations and through the mutated allele in other suggests that this SNP is not causal to CL/P.