Browsing by Author "Suazo, Jose"

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    Association 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, Rafael
    Nonsyndromic 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.
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    Association 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, Rafael
    Objective: To assess the possible association between TGFB3 allele variants and nonsyndromic cleft lip with or without cleft palate in a Chilean population.
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    Maternal genotypes of folate/one-carbon metabolism gene variants and nonsyndromic cleft lip with or without cleft palate risk in Chile
    (2021) Inostroza, Veronica; Salamanca, Carlos; Recabarren, Andrea S.; Pantoja, Roberto; Leiva, Noemi; Pardo, Rosa; Suazo, Jose
    The aim of this study was to evaluate, in a case-control design, the association between maternal genotypes for variants in 23 genes involved in folate/one-carbon metabolism and nonsyndromic cleft lip with or without cleft palate (NSCL/P) in a Chilean population. After applying several filters to an Illumina array, we extracted 175 single nucleotide polymorphisms (SNPs) from 150 mothers of NSCL/P cases and 150 control women. Association was evaluated using computed odds ratio (OR) with a 95% confidence interval (95% CI) in additive, recessive, and dominant models. After multiple comparison correction, only SNP rs4451422 (A>C), located 237 bp downstream of the gene encoding the human folylpolyglutamate synthetase (FPGS), maintained a significant association with NSCL/P in the offspring (OR 3.03; 95% CI 1.69-5.26). The variant rs4451422 is associated with a decrease in FPGS expression according to database annotation. Our results lead to a new hypothesis that a lower activity of FPGS enzyme reduces intracellular folate levels and increases the risk of an offspring having NSCL/P.
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    Parent-of-Origin Effects for MSX1 in a Chilean Population With Nonsyndromic Cleft Lip/Palate
    (WILEY, 2010) Suazo, Jose; Luis Santos, Jose; Jara, Lilian; Blanco, Rafael
    Based 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.