Browsing by Author "Blanco, Rafael"
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- ItemAssociation Between Bone Morphogenetic Protein 4 Gene Polymorphisms with Nonsyndromic Cleft Lip with or without Cleft Palate in a Chilean Population(MARY ANN LIEBERT, INC, 2010) Suazo, Jose; Luis Santos, Jose; Jara, Lilian; Blanco, RafaelNonsyndromic cleft lip with or without cleft palate (NSCLP) is one of the most common birth defects in humans with both genetic and environmental components involved in its expression. Experimental evidences have postulated that bone morphogenetic protein 4 gene (Bmp4) is involved in the etiology of cleft lip with or without cleft palate (CL/P) in mice. In our study we analyzed the association between BMP4 and NSCLP in a sample of 150 unrelated trios ascertained through affected probands. Three BMP4 polymorphisms were analyzed, two intronic (rs762642 and rs2855532) and rs1957860, located 5.7 kb upstream from BMP4. Transmission/disequilibrium tests were performed at the allele and haplotype levels. Our results did not detect preferential transmission for individual single-nucleotide polymorphisms. Significant transmission distortion was observed for haplotypes rs1957860-rs762642 (p = 0.18), especially for C-T (p = 0.015) and T-T (p = 0.018) which include the genomic region where the promoter and an enhancer of BMP4 are located. Thus, despite the positive association detected between these haplotypes and NSCLP they probably do not have a functional effect on BMP4 expression or protein activity but possibly reflect NSCLP susceptibility changes which are in linkage disequilibrium with these polymorphisms. The findings of our study support a role for BMP4 in NSCLP in the admixed Chilean population.
- ItemAssociation Between TGFB3 and Nonsyndromic Cleft Lip With or Without Cleft Palate in a Chilean Population(ALLIANCE COMMUNICATIONS GROUP DIVISION ALLEN PRESS, 2010) Suazo, Jose; Luis Santos, Jose; Scapoli, Luca; Jara, Lilian; Blanco, RafaelObjective: To assess the possible association between TGFB3 allele variants and nonsyndromic cleft lip with or without cleft palate in a Chilean population.
- ItemEstudio de asociación de base familiar entre polimorfismos de MTHFR y mielomeningocele en Chile(2014) Pardo, Rosa; Suazo, José; Castillo, Silvia; Vargas, Marcela; Zalavaria, Andrea; Santos Martín, José Luis; Blanco, Rafael; Rotter, Karin; Solar, Margarita; Tapia, Eva
- ItemLinkage Disequilibrium Between IRF6 Variants and Nonsyndromic Cleft Lip/Palate in the Chilean Population(2008) Suazo, José; Santos Martín, José Luis; Jara, Lilian; Blanco, Rafael
- ItemParent-of-Origin Effects for MSX1 in a Chilean Population With Nonsyndromic Cleft Lip/Palate(WILEY, 2010) Suazo, Jose; Luis Santos, Jose; Jara, Lilian; Blanco, RafaelBased on association and sequencing studies, investigators have postulated muscle segment homeobox 1 (MSX1) as a strong candidate gene involved in the causation of nonsyndromic cleft lip with or without cleft palate (NSCLP). Parent-of-origin effects have been suggested for some NSCLP candidate genes but not for MSX1. The aims of the present study were to test for allele/haplotype associations applying the transmission disequilibrium test (TDT) and the transmission asymmetry test (TAT) to evaluate the possible parent-of-origin effects of MSX1 in Chilean patients with NSCLP. We analyzed five SNPs (rs64466931c.-425G> T/c.-35G>A/rs3775261/rs12532) located from 6.3 kb upstream to 3' UTR in a sample of 150 unrelated NSCLP case-parent trios. Four haplotypes showed overtransmission from parents to affected progeny, but individual SNPs did not. Two haplotypes presented allele combination C-G-A-G (P=0.035) and two T-G-C-A (P=0.044) (SNP order rs64466931c.-35G>A/rs3775261/rs12532). The rs12532 A allele had a 2.08-fold increase in the risk of NSCLP when inherited from the father (95% CI: 1.10-4.02; P=0.025), but not from the mother. These results could indicate epigenetic control by imprinting in the role of MSX1 in NSCLP. Different authors have proposed that some genes that play a role in NSCLP depend on parental origin. Our findings and those previously reported by our group show that a variety of factors appears to be involved in the association between MSX1 and NSCLP. The full mechanism of MSX1 in the development of NSCLP has not been fully understood. (C) 2010 Wiley-Liss, Inc.
- ItemThe BARD1 Cys557Ser variant and risk of familial breast cancer in a South-American population(2012) Gonzalez-Hormazabal, Patricio; Reyes, José M.; Blanco, Rafael; Bravo, Teresa; Carrera, Ignacio; Peralta, Octavio; Gómez, Fernando; Waugh, Enrique; Margarit, Sonia; Ibañez, Gladys; Santos Martín, José Luis; Jara, LilianSince the discovery of the BRCA1 and BRCA2 genes, much work has been carried out to identify further breast cancer (BC) susceptibility genes. BARD1 (BRCA1-associated ring domain) was originally identified as a BRCA1-interacting protein but has also been described in tumor-suppressive functions independent of BRCA1. Some association studies have suggested that the BARD1 Cys557Ser variant might be associated with increased risk of BC, but others have failed to confirm this finding. To date, this variant has not been analyzed in Spanish or South-American populations. In this study, using a case-control design, we analyzed the C-terminal Cys557Ser change in 322 Chilean BC cases with no mutations in BRCA1 or BRCA2 and in 570 controls in order to evaluate its possible association with BC susceptibility. BARD1 Cys557Ser was associated with an increased BC risk (P = 0.04, OR = 3.4 [95 % CI 1.2-10.2]) among cases belonging to families with a strong family history of BC. No difference between single cases affected with age < 50 years at diagnosis (n = 117) and controls was observed for carriers of Cys/Ser genotype. It is likely that this variant is not involved in BC risk in this group of women. We also analyzed a possible interaction between BARD1 557Ser/XRCC3 241Met variants considering the role of both genes in the maintenance of genome integrity. The combined genotype Cys/Ser-carrier with the XRCC3 241Met allele was associated with an increased BC risk (P = 0.02, OR = 5.01 [95 % CI 1.36-18.5]) among women belonging to families with at least three BC and/or ovarian cancer cases. Our results suggest that BARD1 557Ser and XRCC3 241Met may play roles in BC risk in women with a strong family history of BC. Nevertheless there is no evidence of an interaction between the two SNPs. These findings should be confirmed by other studies and in other populations.