C3 Gene Functional Polymorphisms and C3 Serum Levels in Patients with Rheumatoid Arthritis. 2021

Leia Sena, and Camila F Oliveira-Toré, and Thelma Skare, and Iara Jose de Messias-Reason, and Fabiana Antunes Andrade
Laboratory of Molecular Immunopathology, Clinic Hospital, Federal University of Paraná, Curitiba, Brazil.

The complement system is a key component of the innate immunity that plays a significant role in the development and clinical presentation of Rheumatoid arthritis (RA). Complement protein C3 is a central molecule in the activation of complement with a significant role in the inflammatory processes of RA. Nevertheless, the impact of C3 gene polymorphisms in the development of RA is still unknown. The current study aimed to investigate the possible influence of C3 gene polymorphisms in the susceptibility and clinical expression of RA. Three C3 polymorphisms (rs2250656:A > G, intron 2; rs2230199:C > G [p.Arg102Gly], exon 3 and rs1047286:C > T [p.Pro314Leu], exon 9) were assessed by sequence-specific PCR in a total of 156 RA patients and 270 healthy controls from Southern Brazil. In addition, C3 levels were measured in 60 patients and 60 controls by immunoturbidimetry and clinical features were collected from medical records. The frequency of rs2230199 G allele and GG genotype was significantly higher in RA patients than controls (padj = 0.012 OR = 1.57 [1.11-2.31]; padj = 0.008, OR = 1.60 [1.35-2.33]) as well as the rs1047286 T and TT (padj = 0.010, OR = 1.67 [1.12-2.40]; padj = 0.001, OR = 1.83 [1.27-2.65] and the C3 AGT haplotype (padj = 0.0007 OR = 1.92 [1.32-2.80]). Moreover, C3 serum levels were higher in patients than controls (median: 169 mg/dl vs.155 mg/dl; padj = 0.022), as well as in RF seronegative compared with seropositive patients (172 mg/dl vs. 165 mg/dl; padj = 0.007). Our results suggest that the rs2230199 G (p.102Gly) and rs1047286 T (p.314Leu) alleles play a role in the pathophysiology of RA, possibly impacting complement activation by the alternative pathway.

UI MeSH Term Description Entries
D003176 Complement C3 A glycoprotein that is central in both the classical and the alternative pathway of COMPLEMENT ACTIVATION. C3 can be cleaved into COMPLEMENT C3A and COMPLEMENT C3B, spontaneously at low level or by C3 CONVERTASE at high level. The smaller fragment C3a is an ANAPHYLATOXIN and mediator of local inflammatory process. The larger fragment C3b binds with C3 convertase to form C5 convertase. C3 Complement,C3 Precursor,Complement 3,Complement C3 Precursor,Complement Component 3,Precursor-Complement 3,Pro-C3,Pro-Complement 3,C3 Precursor, Complement,C3, Complement,Complement, C3,Component 3, Complement,Precursor Complement 3,Precursor, C3,Precursor, Complement C3,Pro C3,Pro Complement 3
D005787 Gene Frequency The proportion of one particular in the total of all ALLELES for one genetic locus in a breeding POPULATION. Allele Frequency,Genetic Equilibrium,Equilibrium, Genetic,Allele Frequencies,Frequencies, Allele,Frequencies, Gene,Frequency, Allele,Frequency, Gene,Gene Frequencies
D005838 Genotype The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS. Genogroup,Genogroups,Genotypes
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000483 Alleles Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product. Allelomorphs,Allele,Allelomorph
D001172 Arthritis, Rheumatoid A chronic systemic disease, primarily of the joints, marked by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Etiology is unknown, but autoimmune mechanisms have been implicated. Rheumatoid Arthritis
D016022 Case-Control Studies Comparisons that start with the identification of persons with the disease or outcome of interest and a control (comparison, referent) group without the disease or outcome of interest. The relationship of an attribute is examined by comparing both groups with regard to the frequency or levels of outcome over time. Case-Base Studies,Case-Comparison Studies,Case-Referent Studies,Matched Case-Control Studies,Nested Case-Control Studies,Case Control Studies,Case-Compeer Studies,Case-Referrent Studies,Case Base Studies,Case Comparison Studies,Case Control Study,Case Referent Studies,Case Referrent Studies,Case-Comparison Study,Case-Control Studies, Matched,Case-Control Studies, Nested,Case-Control Study,Case-Control Study, Matched,Case-Control Study, Nested,Case-Referent Study,Case-Referrent Study,Matched Case Control Studies,Matched Case-Control Study,Nested Case Control Studies,Nested Case-Control Study,Studies, Case Control,Studies, Case-Base,Studies, Case-Comparison,Studies, Case-Compeer,Studies, Case-Control,Studies, Case-Referent,Studies, Case-Referrent,Studies, Matched Case-Control,Studies, Nested Case-Control,Study, Case Control,Study, Case-Comparison,Study, Case-Control,Study, Case-Referent,Study, Case-Referrent,Study, Matched Case-Control,Study, Nested Case-Control
D020022 Genetic Predisposition to Disease A latent susceptibility to disease at the genetic level, which may be activated under certain conditions. Genetic Predisposition,Genetic Susceptibility,Predisposition, Genetic,Susceptibility, Genetic,Genetic Predispositions,Genetic Susceptibilities,Predispositions, Genetic,Susceptibilities, Genetic
D020641 Polymorphism, Single Nucleotide A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population. SNPs,Single Nucleotide Polymorphism,Nucleotide Polymorphism, Single,Nucleotide Polymorphisms, Single,Polymorphisms, Single Nucleotide,Single Nucleotide Polymorphisms

Related Publications

Leia Sena, and Camila F Oliveira-Toré, and Thelma Skare, and Iara Jose de Messias-Reason, and Fabiana Antunes Andrade
July 2019, Journal of cellular physiology,
Leia Sena, and Camila F Oliveira-Toré, and Thelma Skare, and Iara Jose de Messias-Reason, and Fabiana Antunes Andrade
January 2016, PloS one,
Leia Sena, and Camila F Oliveira-Toré, and Thelma Skare, and Iara Jose de Messias-Reason, and Fabiana Antunes Andrade
June 2018, Clinical rheumatology,
Leia Sena, and Camila F Oliveira-Toré, and Thelma Skare, and Iara Jose de Messias-Reason, and Fabiana Antunes Andrade
February 2017, Scandinavian journal of immunology,
Leia Sena, and Camila F Oliveira-Toré, and Thelma Skare, and Iara Jose de Messias-Reason, and Fabiana Antunes Andrade
January 1987, Human heredity,
Leia Sena, and Camila F Oliveira-Toré, and Thelma Skare, and Iara Jose de Messias-Reason, and Fabiana Antunes Andrade
October 2014, The Eurasian journal of medicine,
Leia Sena, and Camila F Oliveira-Toré, and Thelma Skare, and Iara Jose de Messias-Reason, and Fabiana Antunes Andrade
June 1986, Disease markers,
Leia Sena, and Camila F Oliveira-Toré, and Thelma Skare, and Iara Jose de Messias-Reason, and Fabiana Antunes Andrade
May 2020, International journal of environmental research and public health,
Leia Sena, and Camila F Oliveira-Toré, and Thelma Skare, and Iara Jose de Messias-Reason, and Fabiana Antunes Andrade
January 2000, Tissue antigens,
Leia Sena, and Camila F Oliveira-Toré, and Thelma Skare, and Iara Jose de Messias-Reason, and Fabiana Antunes Andrade
January 1981, Archives roumaines de pathologie experimentales et de microbiologie,
Copied contents to your clipboard!