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Serum amyloid A1 (SAA1) gene polymorphisms in Japanese patients with adult-onset Still's disease.

ABSTRACT: Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder in which inflammasome activation plays a pathophysiological role. In view of the inflammatory nature of AOSD, we investigated whether serum amyloid A (SAA) gene polymorphisms affect the susceptibility of patients with AOSD.Eighty-seven Japanese patients with AOSD and 200 healthy Japanese subjects were recruited in this study. The genotypes of the -13C/T SNP in the 5'-flanking region of the SAA1 gene (rs12218) and two SNPs within exon 3 of SAA1 (2995C/T and 3010C/T polymorphisms) were determined using polymerase chain reaction fragment length polymorphism (PCR-RFLP) assay in all subjects. In AOSD patients, exons 1, 2, 3, and 10 of the MEFV gene were also genotyped by direct sequencing.The frequency of the SAA1.3 allele was increased in AOSD patients compared with that in healthy subjects (43.1% versus 37.5%), but the difference was not significant. The -13T allele was more frequently observed in AOSD patients than in healthy subjects (50.6% versus 41.0%, P?=?.0336). AOSD patients with the -13T allele had been treated with immunosuppressants more frequently than those without this allele. MEFV mutations were detected in 49 patients with AOSD (49/87, 57.3%). AOSD patients with MEFV variants frequently exhibit macrophage activation syndrome, but the difference was not significant (34.7% versus 18.4%, P?=?.081). Also, there was no significant difference in SAA1?-13C/T allele frequency between AOSD patients with and without MEFV mutations.Our data shows a significant association between T allele of rs12218 and AOSD in Japanese population.

SUBMITTER: Yashiro M

PROVIDER: S-EPMC6310518 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Relationship Between Serum Amyloid A1 (<i>SAA1</i>) Gene Polymorphisms Studies with Obesity in the Saudi Population.

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Monocyte gene expression in adult-onset Still's disease

Project description:Adult-onset Still’s disease (AOSD) is a rare autoinflammatory disease, characterized by fever, rash, arthritis and other systemic inflammatory manifestations like hepatosplenomegaly and serositis. One of the most serious complications AOSD is macrophage activation syndrome (MAS), a life-threatening condition caused by excessive activation of immune system and a cytokine storm. Clinical features of MAS include continuous high fever, hepatosplenomegaly, liver dysfunction, lymphadenopathy, hyperferritinemia, and hemophagocytosis. The prevalence of MAS in AOSD patients is estimated to be between 10–19%, but the mortality rate of AOSD-associated MAS is approximately 10–20%. The precise mechanism by which AOSD develops to MAS remains unclear. There is an unmet need to investigate the pathogenesis of MAS in AOSD in order to identify novel biomarkers and therapeutic targets to improve disease prognosis.

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Neutrophil gene expression in adult-onset Still's disease

Project description:Adult-onset Still’s disease (AOSD) is a rare autoinflammatory disease, characterized by fever, rash, arthritis and other systemic inflammatory manifestations like hepatosplenomegaly and serositis. Neutrophil activation is the hallmark of AOSD. Here we aimed to identify candidate biomarker and to validate its association with clinical manifestations in AOSD. Transcriptome analysis of neutrophils from treatment-naïve active AOSD patients and healthy donors was performed. Using cut-offs of >2.0 fold change with p<0.05, we identified 864 DEGs in neutrophils from patients with active AOSD compared to healthy donors, including 442 and 422 upregulated and downregulated genes in active AOSD, respectively. By gene ontology (GO) analysis, we identified several strongly enriched terms of biological process. The most significantly indicated GO term was neutrophil degranulation.

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[Association of rs4638289 and rs7131332 polymorphisms of the serum amyloid A1 gene with Kawasaki disease].

Project description:ObjectiveTo study the association of the polymorphisms of the serum amyloid A1 (SAA1) gene at rs4638289 and rs7131332 loci with Kawasaki disease (KD) and its complication coronary artery lesion (CAL) in children.MethodsA total of 105 Han children with KD who were hospitalized and treated from 2013 to 2017 were enrolled as the KD group. A total of 100 Han children who underwent physical examination were enrolled as the control group. According to the presence or absence of CAL, the KD group was further divided into a CAL group with 23 children and a non-CAL (NCAL) group with 82 children. Polymerase chain reaction-restriction fragment length polymorphism was used to investigate the polymorphisms of the SAA1 gene at rs4638289 and rs7131332 loci.ResuktsFor the locus rs4638289 of the SAA1 gene, there were no significant differences between the KD and control groups in the genotype frequencies of AA, AT, and TT and the allele frequencies of A and T (P>0.05). But there were significant differences between the CAL and NCAL groups in the genotype frequencies of AA, AT, and TT (P=0.016), while there were no significant differences in the allele frequencies of A and T (P>0.05). AT genotype was a protective factor against CAL (OR=0.276, 95%CI: 0.099-0.772, P=0.011). For the locus rs7131332 of the SAA1 gene, there were no significant differences between the KD and control groups in the genotype frequencies of AA, AG, and GG and the allele frequencies of A and G (P>0.05). There were also no significant differences between the CAL and NCAL groups in the genotype frequencies of AA, AG, and GG and the allele frequencies of A and G (P>0.05).ConclusionsPolymorphisms of the SAA1 gene at loci rs4638289 and rs7131332 are not associated with the onset of KD, while the polymorphism at the locus rs4638289 is associated with CAL in KD patients. KD patients with genotype AT may have a reduced risk of CAL.

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Serum amyloid A1: Structure, function and gene polymorphism.

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Acute Myocarditis Revealing Adult-Onset Still's Disease.

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SAA1 gene polymorphisms in osteoporosis patients.

Project description:Background: Serum amyloid A (SAA1) is an apolipoprotein that maintains glucose and lipid homeostasis. Its polymorphisms are associated with risks of myocardial infarction and coronary artery disease (CAD). Methods: However, little is known about the associations of these polymorphisms with susceptibility to osteoporosis, which we evaluated in this hospital-based case-control study involving 300 osteoporosis patients and 350 controls. Three single-nucleotide polymorphisms (SNPs) (rs183978373, rs12218, and rs10832915) were genotyped using MALDI TOF MS. Results: There were no differences in the rs183978373 and rs12218 polymorphisms between the osteoporosis group and controls. The SAA1 gene rs10832915 polymorphism increased the risk of osteoporosis in our Chinese population. The genotypes of the rs10832915 polymorphism were not significantly associated with clinical parameters (age, body mass index (BMI), high- and low-density lipoprotein (LDL), total cholesterol (TC), and T-score). Haplotype analysis revealed that the ATT haplotype had a significant correlation with a decreased risk of osteoporosis. Conclusion: In conclusion, the SAA1 rs10832915 polymorphism and its haplotypes are associated with osteoporosis, but this finding should be confirmed in large well-designed studies.

| S-EPMC6379510 | biostudies-literature

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