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1.
Esther Mancebo Sierra Carolina Aquilino Ana López Herradón Luis Allende Martínez Jesús Ruíz Contreras Juana Gil Pablo Morales Estela Paz Artal 《Inmunología》2012
Aim
Haemophagocytic lymphohistiocytosis (HLH) is characterised by T cell and macrophage activation and excessive production of inflammatory cytokines. Genetic diagnosis is required to discriminate between primary forms (familial HLH, FHL), due to mutations in genes involved in cytolysis, and secondary forms. We aimed to analyse the genes coding for Munc13-4 (UNC13D) and syntaxin-11 (STX11) proteins in search of mutations that might explain HLH in 5 patients without perforin defects.Materials and methods
Perforin expression was evaluated by flow cytometry, sCD25 was measured by ELISA and NK activity was investigated by the conventional functional assay. Coding regions and exons surroundings were sequenced for PRF1, UNC13D and STX11 genes.Results
P1 and P2 developed severe early-onset HLH, P1 died at 6 months. P3, with a sister who died after HLH, responded well to treatment (HLH-2004), and had a second HLH episode two years later. P2 developed HLH at year 7 while in complete remission after lymphoblastic leukaemia. P4 and P5 were brothers who died at 5 and 6 years old due to an HLH and EBV mononucleosis infection. XLP was discarded because P4 was a girl. P1 and P3 showed mutations in UNC13D previously described as pathogenic. There were no changes in STX11.Conclusions
UNC13D mutations were found in 50% of the HLH families without perforin defects and STX11 defects were not detected. These results agree with published series in which mutations in UNC13D explain up to 50% of FHL without PRF1 mutations, supporting a heterogeneous genetic background for this disease. 相似文献2.
3.
Li Tan Bo Bi Peiwei Zhao Xiaonan Cai Chunhui Wan Jianbo Shao Xuelian He 《BMC medical genetics》2017,18(1):141
Background
Microcephaly is a disorder characterized by severe impairment in brain development, reduced brain and head size. Congenital severe microcephaly is very rare, and NDE1 deletion and genetic mutations are important contributors.Case presentation
Single nucleotide polymorphism (SNP) chromosomal microarray analysis (CMA) and muation screening of NDE1 gene were performed in an 8-month patient with severe congenital microcephaly, and/or his parents. Genetic studies found a 16p13.11 deletion containing NDE1 gene, and a novel NDE1 mutation c.555_556GC?>?CT on the non-deleted homolog, inherited from his phenotypically normal parents, respectively. The 2 bp nucleotide change results in a missense mutation p.K185 N and a nonsense mutation p.Q186X. We also conducted literaturte review to compare the clinical phenotypes of our patient to those of cases previously reported with NDE1 mutations, and found all patients had mental retardation, severe microcephaly, and corpus callosum agenesis.Conclusion
This is the first Chinese reported with microcephaly caused by NDE1 mutations. NDE1 is a critical pathogenetic gene in severe congenital microcephaly. Sequencing NDE1 and CMA in patients with severe congenital microcephaly may be warranted.4.
Background
Phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha, PIK3CA, is one of the most frequently mutated genes in breast cancer, and the mutation status of PIK3CA has clinical relevance related to response to therapy.The aim of our study was to investigate the mutation status of PIK3CA gene and to evaluate the concordance between NGS and SGS for the most important hotspot regions in exon 9 and 20, to investigate additional hotspots outside of these exons using NGS, and to correlate the PIK3CA mutation status with the clinicopathological characteristics of the cohort.Methods
In the current study, next-generation sequencing (NGS) and Sanger Sequencing (SGS) was used for the mutational analysis of PIK3CA in 186 breast carcinomas.Results
Altogether, 64 tumors had PIK3CA mutations, 55 of these mutations occurred in exons 9 and 20. Out of these 55 mutations, 52 could also be detected by Sanger sequencing resulting in a concordance of 98.4 % between the two sequencing methods. The three mutations missed by SGS had low variant frequencies below 10 %. Additionally, 4.8 % of the tumors had mutations in exons 1, 4, 7, and 13 of PIK3CA that were not detected by SGS. PIK3CA mutation status was significantly associated with hormone receptor-positivity, HER2-negativity, tumor grade, and lymph node involvement. However, there was no statistically significant association between the PIK3CA mutation status and overall survival.Conclusions
Based on our study, NGS is recommended as follows: 1) for correctly assessing the mutation status of PIK3CA in breast cancer, especially for cases with low tumor content, 2) for the detection of subclonal mutations, and 3) for simultaneous mutation detection in multiple exons.5.
Keze Ma Mingyu Xie Xiaoguang He Guojun Liu Xiaomei Lu Qi Peng Baimao Zhong Ning Li 《BMC medical genetics》2018,19(1):202
Background
Genetic defects in the mitochondrial aminoacyl-tRNA synthetase are important causes of mitochondrial disorders. VARS2 is one of the genes encoding aminoacyl-tRNA synthetases. Recently, an increasing number of pathogenic variants of VARS2 have been reported.Case presentation
We report the novel compound heterozygous pathogenic VARS2 mutations c.643 C?>?T (p. His215Tyr) and c.1354 A?>?G (p. Met452Val) in a female infant who presented with poor sucking at birth, poor activity, hyporeflexia, hypertonia, persistent pulmonary hypertension of newborn (PPHN), metabolic acidosis, severe lactic acidosis, expansion and hypertrophic cardiomyopathy. These heterozygous mutations were carried individually by the proband’s parents and elder sister; the two mutations segregated in the family and were the cause of the disease in the proband.The c.643 C?>?T (p. His215Tyr) mutation was not described in the ExaC, GNomAD and 1000 Genomes Project databases, and the frequency of c.1354 A?>?G (p. Met452Val) was <?0.001 in these gene databases.The two mutated amino acids were located in a highly conserved region of the VARS2 protein that is important for its interaction with the cognate tRNA. The two missense mutations were predicted by online tools to be damaging and deleterious.Conclusions
Our report expands the spectrum of known pathogenicVARS2 variants associated with mitochondrial disorders in humans.VARS2 deficiency may cause a severe neonatal presentation with structural cardiac abnormalities.6.
Robina Khan Niazi Mette Hollensted Christian Theil Have Niels Grarup Oluf Pedersen Asmat Ullah Gulbin Shahid Wasim Ahmad Asma Gul Torben Hansen 《BMC medical genetics》2018,19(1):199
Background
Mutations in the genes encoding leptin (LEP), the leptin receptor (LEPR), and the melanocortin 4 receptor (MC4R) are known to cause severe early-onset childhood obesity. The aim of the current study was to examine the prevalence of damaging LEP, LEPR, and MC4R mutations in Pakistani families having a recessive heritance of early-onset obesity.Methods
Using targeted resequencing, the presence of rare mutations in LEP, LEPR, and MC4R, was investigated in individuals from 25 families suspected of having autosomal recessive early-onset obesity. Segregation patterns of variants were assessed based on chip-based genotyping.Results
Homozygous LEPR variants were identified in two probands. One carried a deletion (c.3260AG) resulting in the frameshift mutation p.Ser1090Trpfs*6, and the second carried a substitution (c.2675C?>?G) resulting in the missense mutation p.Pro892Arg. Both mutations were located within regions of homozygosity shared only among affected individuals. Both probands displayed early-onset obesity, hyperphagia and diabetes. No mutations were found in LEP and MC4R.Conclusions
The current study highlights the implication of LEPR mutations in cases of severe early-onset obesity in consanguineous Pakistani families. Through targeted resequencing, we identified novel damaging mutations, and our approach may therefore be utilized in clinical testing or diagnosis of known forms of monogenic obesity with the aim of optimizing obesity treatment.7.
Carlos A. Arango-Franco Marcela Moncada-Vélez Claudia Patricia Beltrán Indira Berrío Cristian Mogollón Andrea Restrepo Mónica Trujillo Sara Daniela Osorio Lorena Castro Lina Vanessa Gómez Ana María Muñoz Verónica Molina Delsy Yurledy del Río Cobaleda Ana Cristina Ruiz Carlos Garcés Juan Fernando Alzate Felipe Cabarcas Julio Cesar Orrego Jean-Laurent Casanova Andrés Augusto Arias José Luis Franco 《Journal of clinical immunology》2018,38(7):794-803
Purpose
CARD9 deficiency is an inborn error of immunity that predisposes otherwise healthy humans to mucocutaneous and invasive fungal infections, mostly caused by Candida, but also by dermatophytes, Aspergillus, and other fungi. Phaeohyphomycosis are an emerging group of fungal infections caused by dematiaceous fungi (phaeohyphomycetes) and are being increasingly identified in patients with CARD9 deficiency. The Corynespora genus belongs to phaeohyphomycetes and only one adult patient with CARD9 deficiency has been reported to suffer from invasive disease caused by C. cassiicola. We identified a Colombian child with an early-onset, deep, and destructive mucocutaneous infection due to C. cassiicola and we searched for mutations in CARD9.Methods
We reviewed the medical records and immunological findings in the patient. Microbiologic tests and biopsies were performed. Whole-exome sequencing (WES) was made and Sanger sequencing was used to confirm the CARD9 mutations in the patient and her family. Finally, CARD9 protein expression was evaluated in peripheral blood mononuclear cells (PBMC) by western blotting.Results
The patient was affected by a large, indurated, foul-smelling, and verrucous ulcerated lesion on the left side of the face with extensive necrosis and crusting, due to a C. cassiicola infectious disease. WES led to the identification of compound heterozygous mutations in the patient consisting of the previously reported p.Q289* nonsense (c.865C > T, exon 6) mutation, and a novel deletion (c.23_29del; p.Asp8Alafs10*) leading to a frameshift and a premature stop codon in exon 2. CARD9 protein expression was absent in peripheral blood mononuclear cells from the patient.Conclusion
We describe here compound heterozygous loss-of-expression mutations in CARD9 leading to severe deep and destructive mucocutaneous phaeohyphomycosis due to C. cassiicola in a Colombian child.8.
The aim of this study was molecular identification of Cryptosporidium species and assessment of their prevalence in different breeds of sheep and goat reared in Poland. In addition, the relationship between animal age, breed type, and the frequency of Cryptosporidium infections was determined. Fecal samples from 234 lambs and 105 goat kids aged up to 9 weeks, representing 24 breeds and their cross-breeds were collected from 71 small ruminant farms across Poland. The identification of Cryptosporidium species was performed at the 18 SSU ribosomal RNA (rRNA) and COWP loci followed by subtyping of C. parvum and C. hominis strains at GP60 gene locus. The presence of Cryptosporidium DNA at the 18 SSU rRNA locus was detected in 45/234 (19.2%) lamb feces samples and in 39/105 (37.1%) taken from goats. The following Cryptosporidium species: C. xiaoi, C. bovis, C. ubiquitum, C. parvum, and C. hominis were detected in small ruminants. Infections caused by C. xiaoi were predominant without favoring any tested animal species. Subsequent GP60 subtyping revealed the presence of C. parvum IIaA17G1R1 subtype in sheep and IIdA23G1 subtype in goats. IIdA23G1 subtype was detected in a goat host for the first time. There were no significant differences found in frequency of infections between the age groups (<3 and 3–9 weeks) of lambs (P = 0.14, α > 0.05) or goat kids (P = 0.06, α > 0.05). In addition, there was no correlation observed between the frequency in occurrence of particular parasite species and breed type in relation to native sheep breeds (F = 0.11; P = 0.990 > 0.05). In the case of goats, more breed-related differences in parasite occurrence were found. The results of this study improve our knowledge on the breed-related occurrence of Cryptosporidium infections in the population of small ruminants reared in Poland. 相似文献
9.
Monica Cattaneo Lucia La Sala Maurizio Rondinelli Edoardo Errichiello Orsetta Zuffardi Annibale Alessandro Puca Stefano Genovese Antonio Ceriello 《BMC medical genetics》2017,18(1):147
Background
Mutations in the gene that encodes CDGSH iron sulfur domain 2 (CISD2) are causative of Wolfram syndrome type 2 (WFS2), a rare autosomal recessive neurodegenerative disorder mainly characterized by diabetes mellitus, optic atrophy, peptic ulcer bleeding and defective platelet aggregation. Four mutations in the CISD2 gene have been reported. Among these mutations, the homozygous c.103?+?1G?>?A substitution was identified in the donor splice site of intron 1 in two Italian sisters and was predicted to cause a exon 1 to be skipped.Methods
Here, we employed molecular assays to characterize the c.103?+?1G?>?A mutation using the patient’s peripheral blood mononuclear cells (PBMCs). 5′-RACE coupled with RT-PCR were used to analyse the effect of the c.103?+?1G?>?A mutation on mRNA splicing. Western blot analysis was used to analyse the consequences of the CISD2 mutation on the encoded protein.Results
We demonstrated that the c.103?+?1G?>?A mutation functionally impaired mRNA splicing, producing multiple splice variants characterized by the whole or partial absence of exon 1, which introduced amino acid changes and a premature stop. The affected mRNAs resulted in either predicted targets for nonsense mRNA decay (NMD) or non-functional isoforms.Conclusions
We concluded that the c.103?+?1G?>?A mutation resulted in the loss of functional CISD2 protein in the two Italian WFS2 patients.10.
Hong Il Ha Min-Jeong Kim Jihyun Kim Sun-Young Park Kwanseop Lee Jang Yong Jeon 《Surgical and radiologic anatomy : SRA》2016,38(6):655-662
Purpose
We categorize the subtypes of the replaced common hepatic artery (RCHA) and evaluate the clinical implications.Methods
Thirty-four cases of the RCHA were evaluated retrospectively using multidetector computed tomography. We categorized them into the three RCHA subtypes according to pancreatic penetration and the passing routes. The distance between the orifice of the superior mesenteric artery (SMA) and RCHA bifurcation (D SMA-RCHA) was measured using advanced 3D imaging software. Analysis of variance was used to evaluate the difference in D SMA-RCHA according to the RCHA subtype.Results
Type A (n = 17, 50 %) referred to RCHA penetrating the pancreatic parenchyma, all crossing the dorsal aspect of the superior mesenteric vein (SMV). Among them, three cases were accompanied by the circumportal pancreas. Type B (n = 10, 29 %) referred to RCHA without penetration of the pancreatic parenchyma and crossing of the dorsal aspect of the main portal vein (MPV) or SMV. Type C (n = 7, 21 %) referred to RCHA without penetration of the pancreas parenchyma and crossing of the ventral aspect of the MPV or SMV. The mean D SMA-RCHA of each subtype was as follows: type A, 3.13 cm [95 % confidence interval (CI) 2.70–3.57]; type B, 2.04 cm [95 % CI 1.40–2.68]; and type C, 2.14 cm [95 % CI 2.23–2.92]. The D SMA-RCHA of the penetrating pancreatic parenchyma of the RCHA was significantly longer than that of the non-penetrating pancreatic parenchyma (P = 0.007).Conclusion
Half of RCHA show penetrating the pancreatic parenchyma, which was categorized as type A, and this type A takes off from the SMA more distally than RCHA without intrapancreatic penetration.11.
Agnieszka Pollak Urszula Lechowicz Victor Abel Murcia Pieńkowski Piotr Stawiński Joanna Kosińska Henryk Skarżyński Monika Ołdak Rafał Płoski 《BMC medical genetics》2017,18(1):142
Background
Implementation of whole exome sequencing has provided unique opportunity for a wide screening of causative variants in genetically heterogeneous diseases, including nonsyndromic hearing impairment. TRIOBP in the inner ear is responsible for proper structure and function of stereocilia and is necessary for sound transduction.Methods
Whole exome sequencing followed by Sanger sequencing was conducted on patients derived from Polish hearing loss family.Results
Based on whole exome analysis, we identified two TRIOBP pathogenic variants (c.802_805delCAGG, p.Gln268Leufs*610 and c.5014G>T, p.Gly1672*, the first of which was novel) causative of nonsyndromic, peri- to postlingual, moderate-to-severe hearing loss in three siblings from a Polish family. Typically, TRIOBP pathogenic variants lead to prelingual, severe-to-profound hearing loss, thus the onset and degree of hearing impairment in our patients represent a distinct phenotypic manifestation caused by TRIOBP variants. The pathogenic variant p.Gln268Leufs*610 disrupts the TRIOBP-4 and TRIOBP-5 isoforms (both expressed exclusively in the inner ear and retina) whereas the second pathogenic variant c.514G>T, p.Gly1672* affects only TRIOBP-5.Conclusions
The onset and degree of hearing impairment, characteristic for our patients, represent a unique phenotypic manifestation caused by TRIOBP pathogenic variants. Although TRIOBP alterations are not a frequent cause of hearing impairment, this gene should be thoroughly analyzed especially in patients with a postlingual hearing loss. A delayed onset of hearing impairment due to TRIOBP pathogenic variants creates a potential therapeutic window for future targeted therapies.12.
Naoki Oishi Tetsuo Kondo Tadao Nakazawa Kunio Mochizuki Tomohiro Inoue Kazunari Kasai Ippei Tahara Tomonori Yabuta Mitsuyoshi Hirokawa Akira Miyauchi Ryohei Katoh 《Endocrine pathology》2017,28(2):103-111
Pediatric papillary thyroid carcinoma (PTC) has unique features but requires further genetic investigation. Moreover, there has been increasing concern about the risk for pediatric PTC in Japan after the Fukushima accident. This study aims to evaluate the frequencies of BRAF and TERT promoter mutations and to examine their significance in non-radiation-associated pediatric PTCs in Japan. We enrolled 81 pediatric PTC patients aged ≤20 years. The control group included 91 adult PTCs from patients >20 years old. BRAF and TERT mutations were analyzed by allele-specific-PCR and/or Sanger sequencing. Compared with adult PTCs, pediatric PTCs exhibited larger tumor size, more frequent lymph node metastasis, and less classical histology. The prevalence of BRAF V600E in pediatric PTCs was 54% and significantly lower than that in adults of 85%. In the pediatric PTCs, BRAF V600E was positively associated with older age, classical histology, and the lymph node metastasis but independent from other clinicopathological factors. TERT mutations were identified in 13% of adults and in none of the pediatric PTCs. In conclusion, pediatric PTCs are characterized by more advanced clinicopathological features, lower BRAF V600E frequency, and absence of TERT mutation. The BRAF V600E frequency in this study is similar to the reported BRAF V600E frequency in the ultrasonographically screened pediatric PTCs in Fukushima. 相似文献
13.
Ayoub Aglaguel Houria Abdelghaffar Fatima Ailal Norddine Habti Sebastian Hesse Naschla Kohistani Christoph Klein Ahmed Aziz Bousfiha 《Journal of clinical immunology》2017,37(4):357-362
Purpose
Poikiloderma with Neutropenia (PN) is inherited genodermatosis which results from a biallelic mutation in the USB1 gene (U Six Biogenesis 1). PN, first described in Navajo Native Americans, is characterized by early onset poikiloderma, pachyonychia, palmo-plantar hyperkeratosis, and permanent neutropenia. This condition results in frequent respiratory tract infections during infancy and childhood. From 2011 to 2013, four cases of PN were diagnosed in Morocco. In this paper, we report the first four cases of PN diagnosed in Morocco, out of three unrelated consanguinous families.Methods
We investigated the genetic, immunological, and clinical features of four Moroccan patients with PN from three unrelated consanguinous families.Results
Mean age at onset was 3 months and mean age at diagnosis was 7.5 years. The diagnosis of these PN patients was made based on clinical features and confirmed by molecular analysis for three cases. We identified two undescribed homozygous mutations in the USB1 gene: c.609 + 1G>A in two siblings and c.518 T>G(p.(Leu173Arg)) in the other case.Conclusion
This report confirms the clinical and genetic identity of Poikiloderma with Neutropenia syndrome.14.
X. Wang K. E. Greenwood-Quaintance M. J. Karau D. R. Block J. N. Mandrekar S. A. Cunningham J. M. Mallea R. Patel 《European journal of clinical microbiology & infectious diseases》2017,36(3):517-522
A relationship between hyperammonemia and Ureaplasma infection has been shown in lung transplant recipients. We have demonstrated that Ureaplasma urealyticum causes hyperammonemia in a novel immunocompromised murine model. Herein, we determined whether Ureaplasma parvum can do the same. Male C3H mice were given mycophenolate mofetil, tacrolimus, and prednisone for 7 days, and then challenged with U. parvum intratracheally (IT) and/or intraperitoneally (IP), while continuing immunosuppression over 6 days. Plasma ammonia concentrations were determined and compared using Wilcoxon rank-sum tests. Plasma ammonia concentrations of immunosuppressed mice challenged IT/IP with spent broth (median, 188 μmol/L; range, 102–340 μmol/L) were similar to those of normal (median, 226 μmol/L; range, 154–284 μmol/L, p?>?0.05), uninfected immunosuppressed (median, 231 μmol/L; range, 122–340 μmol/L, p?>?0.05), and U. parvum IT/IP challenged immunocompetent (median, 226 μmol/L; range, 130–330 μmol/L, p?>?0.05) mice. Immunosuppressed mice challenged with U. parvum IT/IP (median 343 μmol/L; range 136–1,000 μmol/L) or IP (median 307 μmol/L; range 132–692 μmol/L) had higher plasma ammonia concentrations than those challenged IT/IP with spent broth (p?<?0.001). U. parvum can cause hyperammonemia in pharmacologically immunocompromised mice. 相似文献
15.
K. Govender G. George S Beckett C. Montague J. Frohlich 《International journal of behavioral medicine》2018,25(1):123-130
Purpose
This study sought to assess risk compensation following voluntary medical male circumcision of young school-going men. Risk compensation is defined as an inadvertent increase in sexual risk behaviors and a corresponding decrease in self-perceived risk for contracting HIV following the application of a risk reduction technology.Methods
This study documented the sexual practices of circumcised (n = 485) and uncircumcised (n = 496) young men in 42 secondary schools at three time points (baseline and 6 and 12 months) in a sub-district of KwaZulu-Natal, South Africa. Study participants were aged from 16 to 24 years old.Results
At the end of the study period, there was no significant difference between the two cohorts concerning learners’ perceptions of being at risk of contracting HIV (interaction effect: b = ?0.12, p = 0.40). There was also no significant difference in the number of sexual partners in the previous month (interaction effect: b = ?0.23, p = 0.15). The proportion of learners who have never used a condom decreased significantly over time (time effect: b = ?0.27, p = 0.01), and there was no difference between the circumcised and uncircumcised learners (interaction effect: b = ?0.09, p = 0.91).Conclusions
Risk compensation, as evidenced in this study over a 1-year period, was not associated with undergoing voluntary medical male circumcision (VMMC) in our sample of young school-going men. However, it is of concern that at the end of this study, less than half of the sexually active sample in a high-HIV-prevalence community used condoms consistently in the previous month (39% for both study cohorts). The latter underscores the need to view VMMC as a potential entry point for planned HIV and sexuality education interventions targeting young men in this community.16.
17.
Yufeng Qian Genlin Wang Feng Xue Lianghui Chen Yan Wang Liang Tang Huilin Yang 《Inflammation research》2017,66(8):653-661
Objectives
Ankylosing spondylitis (AS) is a chronic inflammatory joint disease. The transporter associated with antigen processing (TAP) has been identified to play an important role in immune response as well as the HLA-associated diseases. The aim of our meta-analysis was to investigate the contribution of TAP (TAP1 and TAP2) polymorphisms to the risk of AS.Methods
Meta-analyses were performed between 2 polymorphisms in TAP1 (TAP1-333, -637) and 3 polymorphisms in TAP2 (TAP2-379, -565, and -665) and AS.Results
The meta-analyses were involved with 6 studies with 415 cases and 659 controls. Significant association was found between TAP1-333Val, TAP1-637Gly, and TAP2-565Thr and AS compared with combined control group (TAP1-333Val: p = 0.009, OR = 1.40, 95% CI 1.09–1.80; TAP1-637Gly: p = 0.002, OR = 1.48, 95% CI 1.15–1.91; p = 0.03, OR = 1.38, 95% CI 1.04–1.84). Subgroup analysis shown that significant association was only found in AS when compared with HLA-B27-negative controls (TAP1-333Val: p = 0.004, OR = 1.53, 95% CI 1.14–2.06; TAP1-637Gly: p = 0.004, OR = 1.52, 95% CI 1.15–2.02; p = 0.02, OR = 1.56, 95% CI 1.09–2.24), but not in AS when compared with HLA-B27-positive controls (p > 0.05). Moreover, no significant associations were found between haplotypes in TAP1 and TAP2 in both the combined and the subgroup analyses (p > 0.05).Conclusions
TAP1-333Val, TAP1-637Gly, and TAP2-565Thr were likely to be associated with AS.18.
Hector Gonzalez-Pacheco Gilberto Vargas-Alarcon Javier Angeles-Martinez Carlos Martinez-Sanchez Oscar Perez-Mendez Gabriel Herrera-Maya Marco Antonio Martinez-Rios Marco Antonio Peña-Duque Carlos Posadas-Romero Jose Manuel Fragoso 《Immunologic research》2017,65(4):862-868
The protein products of NLRP3 and CASP1 genes are involved in the cleavage of pro-IL-1B and pro-IL-18 leading to the active cytokines, which play an important role in the development of the acute coronary syndrome (ACS). The aim of the present study was to evaluate whether NLRP3 and CASP1 gene polymorphisms are biomarkers of ACS susceptibility in Mexican population. Two polymorphisms of the CASP1 gene [G+7/in6A (rs501192) and A10370-G Exon-6 (rs580253)] and one of the NLRP3 gene [UTR′3 G37562-C (rs10754558)] were genotyped by 5′ exonuclease TaqMan assays in a group of 617 patients with ACS and 609 control individuals. Under recessive model, the CASP1 G+7/in6A polymorphism was associated with an increased risk of developing ACS when compared to healthy controls (OR = 1.76, 95% CI 1.08–2.86, P Res = 0.022). In the same way, under recessive model, the CASP1 A10370-G was associated with increased risk of ACS (OR = 1.75, 95% CI 1.07–2.85, P Res = 0.025). Moreover, under co-dominant, dominant, over-dominant, and additive models, the NLRP3 UTR′3 G37562-C was associated with a decreased risk of ACS (OR = 0.45, 95%CI 0.22–0.92, P Co-dom = 0.006; OR = 0.61, 95%CI 0.44–0.84, P Dom = 0.002; OR = 0.67, 95%CI 0.48–0.94, P Over-dom = 0.02; and OR = 0.65, 95%CI 0.50–0.94, P Add = 0.02, respectively). In summary, this study demonstrates that the G+7/in6A and A10370-G polymorphisms of the CASP1 gene are associated with increased risk of developing ACS, whereas the UTR′3 G37562-C polymorphism of the NLRP3 gene is associated with a decreased risk of developing ACS in Mexican population. 相似文献
19.
Hans-Juergen Schulten Mohammed Bangash Sajjad Karim Ashraf Dallol Deema Hussein Adnan Merdad Fatma K. Al-Thoubaity Jaudah Al-Maghrabi Awatif Jamal Fahad Al-Ghamdi Hani Choudhry Saleh S. Baeesa Adeel G. Chaudhary Mohammed H. Al-Qahtani 《Journal of translational medicine》2017,15(1):269