IMBICE   05372
INSTITUTO MULTIDISCIPLINARIO DE BIOLOGIA CELULAR
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Association between rs642961 and cleft lip and palate in Patagonia (ECLAMC) population
Autor/es:
CARVALHO FM, VIEIRA AR, POLETTA FA, MEREB JC, FONSECA RF, LOPEZ CAMELO JS, CASTILLA EE, ORIOLI I
Lugar:
Buenos Aires
Reunión:
Encuentro; 37th Clearinghouse Annual Meeting and 42a Reunion Anual del ECLAMC; 2011
Institución organizadora:
Clearinghouse
Resumen:
Association between rs642961 and cleft lip and palate in Patagonia (ECLAMC)
population. F. M. de Carvalho1, A. R. Vieira2,3,4,
F. Poletta5,6, J. C. Mereb7, R. F. Fonseca1, J.
L. Camelo5,6,8, E. E. Castilla5,6,9, I. M.
Orioli1 1) ECLAMC and INAGEMP at Genetics Department, Federal
University of Rio de Janeiro, RJ, Brazill; 2) Department of Oral Biology, School
of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA; 3) Pediatric
Dentistry Department, School of Dental Medicine, University of Pittsburgh,
Pittsburgh, PA, USA; 4) Center for Craniofacial and Dental Genetics, School of
Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA; 5) ECLAMC and
INAGEMP at CEMIC (Center for Medical Education and Clinical Research), Buenos
Aires, Argentina; 6) CONICET (National Research Council of Argentina), Buenos
Aires, Argentina; 7) ECLAMC and INAGEMP at Hospital Zonal El Bolson, El Bolson,
Rio Negro, Argentina; 8) ECLAMC at IMBICE /CONICET, La Plata, Argentina; 9)
ECLAMC and INAGEMP at Epidemiology Laboratory of Congenital Malformations,
Oswaldo Cruz Institute, Rio de Janeiro, Brazil.
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.