A predicted functional single-nucleotide polymorphism of bone morphogenetic protein-4 gene affects mRNA expression and shows a significant association with cutaneous melanoma in Southern Italian population

Capasso, Mario; Ayala, Fabrizio; Russo, Roberta; Avvisati, Rosa Anna; Asci, Roberta; Iolascon, Achille

doi:10.1007/s00432-009-0628-y

Cited by 30 publications

(30 citation statements)

References 30 publications

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“…Melanoma risk is determined by a large number of variables. We have recently demonstrated that a predict functional SNP of BMP4 could influence the susceptibility to CM 26 and other genetic associations with the risk of CM have been found. 27 The association between MDM2 SNP309 and tumor risk has been evaluated in diverse populations including diverse tumor types (lung, breast, colorectal, bladder, ovarian and so on).…”

Section: Discussionmentioning

confidence: 96%

MDM2 SNP309 and p53 Arg72Pro in cutaneous melanoma: association between SNP309 GG genotype and tumor Breslow thickness

et al. 2010

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A functional single nucleotide polymorphism (SNP) 309 T/G within mouse double minute 2 (MDM2) gene has been linked to onset and outcome of disease in tumors. Two published studies have shown discordant results regarding the effect of this SNP on age at diagnosis of cutaneous melanoma (CM) in Caucasian female populations. Here, we examined the age at diagnosis and clinical associations of CM with SNP309 and the related polymorphism, p53 Arg72Pro, in an Italian population (249 CM patients and 291 cancer-free controls) composed of women and men. MDM2 intronic region of 294 bp was directly sequenced, whereas Arg72Pro SNP was analyzed by polymerase chain reaction-restriction fragment length polymorphism. No associations were found among the SNP309, Arg72Pro, risk of CM, age at diagnosis and presence of metastasis in total subjects and when stratified according to the gender. The SNP309 was significantly associated with tumor Breslow thickness. The P-value in the minor allele recessive mode was 0.02, and the odds ratio (OR) adjusted for gender and age was 3.11 (95% confidential interval (CI)¼1.21-8.00). The SNP309 is not associated with the risk and age of onset of CM, and the presence of metastasis in an Italian population but the SNP309 GG may be a risk genotype for increasing in tumor Breslow thickness.

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Section: Discussionmentioning

confidence: 96%

MDM2 SNP309 and p53 Arg72Pro in cutaneous melanoma: association between SNP309 GG genotype and tumor Breslow thickness

et al. 2010

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“…Non-synonymous SNPs are always evaluated for their effect on protein stability and/or function. Some investigations have reported the impact on the transcriptional process and mRNA stability as a result of non-synonymous SNPs [68], [69]. To determine whether this SNP may modulate the expression of this gene and influence the structure or function of the related protein, real-time PCR analysis and functional prediction of non-synonymous SNP were performed.…”

Section: Discussionmentioning

confidence: 99%

A Post-GWAS Replication Study Confirming the PTK2 Gene Associated with Milk Production Traits in Chinese Holstein

Wang

Jiang

et al. 2013

PLoS ONE

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Our initial genome-wide association study (GWAS) demonstrated that two SNPs (ARS-BFGL-NGS-33248, UA-IFASA-9288) within the protein tyrosine kinase 2 (PTK2) gene were significantly associated with milk production traits in Chinese Holstein dairy cattle. To further validate if the statistical evidence provided in GWAS were true-positive findings, a replication study was performed herein through genotype-phenotype associations. The two tested SNPs were found to show significant associations with milk production traits, which confirmed the associations observed in the original study. Specifically, SNPs lying in the PTK2 gene were also detected by sequencing 14 unrelated sires in Chinese Holsteins and a total of thirty-three novel SNPs were identified. Thirteen out of these identified SNPs were genotyped and tested for association with milk production traits in an independent resource population. After Bonferroni correction for multiple testing, twelve SNPs were statistically significant for more than two milk production traits. Analyses of pairwise D’ measures of linkage disequilibrium (LD) between all SNPs were also explored. Two haplotype blocks were inferred and the association study at haplotype level revealed similar effects on milk production traits. In addition, the RNA expression analyses revealed that a non-synonymous coding SNP (g.4061098T>G) was involved in the regulation of gene expression. Thus the findings presented here provide strong evidence for associations of PTK2 variants with dairy production traits and may be applied in Chinese Holstein breeding program.

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“…The results showed more negative predicted free energy for Haplotype 2 compared with Haplotype 1, which appeared to predominantly result from effects of the rs3814058 t>c SNP. More negative free energy should lead to a more stable structure with less mRNA degradation and higher levels of Haplotype 2 mRNA compared with Haplotype 1 mRNA, as has been previously reported for SNPs in several other genes (Capasso et al 2009; Wang et al 2005; Wang and Sadee 2006). In support of this contention we observed higher PXR -3′UTR mRNA levels in those individuals that carried the rs3814058 SNP (including Haplotype 2).…”

Section: Discussionmentioning

confidence: 57%

Identification of polymorphisms in the 3′-untranslated region of the human pregnane X receptor (PXR) gene associated with variability in cytochrome P450 3A (CYP3A) metabolism

et al. 2010

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Single nucleotide polymorphisms (SNPs) in the 3′untranslated region (3′UTR) of human pregnane X receptor (PXR) gene may contribute to interindividual variability in cytochrome P450 3A (CYP3A) activity. Genotype-phenotype associations involving PXR-3′UTR SNPs were investigated through in vitro (53 human livers from primarily white donors) and in vivo (26 white or African-American volunteers) studies using midazolam 1′-hydroxylation and midazolam apparent oral clearance (CL/F), respectively, as CYP3A-specific probes. PXR-3′UTR resequencing identified 12 SNPs, including 2 that were novel. Although none of the SNPs evaluated were associated with altered midazolam 1′-hydroxylation in the liver bank, both rs3732359 homozygotes and rs3732360 carriers showed 80% higher (P<0.05) CL/F compared with homozygous reference individuals. These differences in CL/F were even larger (100 and 120% higher, respectively; P<0.01) when only African-American subjects (n=14) were considered. Five major haplotypes were identified containing the PXR-3′UTR SNPs and previously identified intron SNPs. Although CL/F differences were not statistically significant within the entire study cohort, African-American carriers of Haplotype-1 (which includes both rs3732359 and rs3732360 variants) exhibited 70% higher median CL/F compared with African-American non-carriers (P=0.036). Our results identify rs3732359 and rs3732360 as PXR-3′UTR SNPs associated with higher CYP3A activity in vivo in African-Americans.

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A predicted functional single-nucleotide polymorphism of bone morphogenetic protein-4 gene affects mRNA expression and shows a significant association with cutaneous melanoma in Southern Italian population

Abstract: This study evidences the relevance of using bioinformatics tools in searching for cancer-associated gene polymorphisms and suggests that the predicted functional SNP 6007 C/T affects BMP4 gene expression and the risk to development of CM.

Cited by 30 publications

References 30 publications

MDM2 SNP309 and p53 Arg72Pro in cutaneous melanoma: association between SNP309 GG genotype and tumor Breslow thickness

MDM2 SNP309 and p53 Arg72Pro in cutaneous melanoma: association between SNP309 GG genotype and tumor Breslow thickness

A Post-GWAS Replication Study Confirming the PTK2 Gene Associated with Milk Production Traits in Chinese Holstein

Identification of polymorphisms in the 3′-untranslated region of the human pregnane X receptor (PXR) gene associated with variability in cytochrome P450 3A (CYP3A) metabolism

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