@article {3502, title = {Novel missense mutation in the NOD2 gene in a patient with early onset ulcerative colitis: causal or chance association?}, journal = {Int J Mol Sci}, volume = {15}, year = {2014}, month = {2014}, pages = {3834-41}, abstract = {

Deregulated immune response to gut microflora in genetically predisposed individuals is typical for inflammatory bowel diseases. It is reasonable to assume that genetic association with the disease will be more pronounced in subjects with early onset than adult onset. The nucleotide-binding oligomerization domain containing-2 gene, commonly involved in multifactorial risk of Crohn{\textquoteright}s disease, and interleukin 10 receptor genes, associated with rare forms of early onset inflammatory bowel diseases, were sequenced in an early onset patient. We identified a novel variant in the NOD2 gene (c.2857A > G p.K953E) and two already described missense variants in the IL10RA gene (S159G and G351R). The new NOD2 missense variant was examined in silico with two online bioinformatics tools to predict the potentially deleterious effects of the mutation. Although cumulative effect of these variations in the early onset of the disease can be only hypothesized, we demonstrated that family information and in silico studies can be used to predict association with the disease.

}, keywords = {Age of Onset, Amino Acid Sequence, Base Sequence, Child, Colitis, Ulcerative, Crohn Disease, DNA Mutational Analysis, Genetic Predisposition to Disease, Genotype, Humans, Interleukin-10 Receptor alpha Subunit, Interleukin-10 Receptor beta Subunit, Molecular Sequence Data, Mutation, Missense, Nod2 Signaling Adaptor Protein, Polymorphism, Single Nucleotide, Risk Factors, Sequence Homology, Amino Acid}, issn = {1422-0067}, doi = {10.3390/ijms15033834}, author = {Girardelli, Martina and Vuch, Josef and Tommasini, Alberto and Crovella, Sergio and Bianco, Anna Monica} } @article {1971, title = {NLRP1 polymorphisms in patients with asbestos-associated mesothelioma.}, journal = {Infect Agent Cancer}, volume = {7}, year = {2012}, month = {2012}, pages = {25}, abstract = {

UNLABELLED:

BACKGROUND: An increasing incidence of malignant mesothelioma (MM) cases in patients with low levels of asbestos exposure suggests the interference of alternative cofactors. SV40 infection was detected, as co-morbidity factor, only in 22\% of asbestos-MM patients from a North-Eastern Italy area. An additional mechanism of injury related to asbestos exposure in MM development has been recently associated to inflammatory responses, principally driven by interleukin (IL)-1 beta ({\ss}) activated within the inflammasome complex.NLRP3 inflammosome has been described as the intracellular sensor for asbestos able to induce inflammasome activation and IL-1{\ss} secretion while NLRP1 is expressed in lung epithelial cells and alveolar macrophages and contributes to the immune response and to survival/apoptosis balance. This study proposes to evaluate the impact of known NLRP3 and NLRP1 polymorphisms in the individual susceptibility to asbestos-induced mesothelioma in subjects from a hyperendemic area for MM.

METHODS: 134 Italian patients with diagnosis of mesothelioma due (MMAE, n=69) or not (MMAF, n=65) to asbestos, 256 healthy Italian blood donors and 101 Italian healthy subjects exposed to asbestos (HCAE) were genotyped for NLRP1 (rs2670660 and rs12150220) and NLRP3 (rs35829419 and rs10754558) polymorphisms.

RESULTS: While NLRP3 SNPs were not associated to mesothelioma, the NLRP1 rs12150220 allele T was significantly more frequent in MMAE (0.55) than in HCAE (0.41) (p=0.011; OR=1.79) suggesting a predisponent effect of this allele on the development of mesothelioma. This effect was amplified when the NLRP1 rs2670660 allele was combined with the NLRP1 rs12150220 allele (p=0.004; OR=0.52).

CONCLUSION: Although NLRP3 SNPs was not involved in mesothelioma predisposition, these data proposed NLRP1 as a novel factor possibly involved in the development of mesothelioma.

}, issn = {1750-9378}, doi = {10.1186/1750-9378-7-25}, author = {Girardelli, Martina and Maestri, Iva and Rinaldi, Rosa R and Tognon, Mauro and Boldorini, Renzo and Bovenzi, Massimo and Crovella, Sergio and Comar, Manola} }