Li Shen1, Hui Zhang2, Xindie Zhou2, Ruiping Liu3. 1. Department of Clinical Laboratory, Changzhou First People's Hospital, Changzhou 213003, China. 2. Department of Orthopaedics, Affiliated Hospital of Nanjing Medical University, Changzhou Second People's Hospital, Changzhou 213003, China. 3. Department of Orthopaedics, Affiliated Hospital of Nanjing Medical University, Changzhou Second People's Hospital, Changzhou 213003, China; Central Laboratory, Changzhou Second People's Hospital, Affiliated Hospital of Nanjing Medical University, Changzhou 213003, China. Electronic address: lrp216@sina.com.
Abstract
INTRODUCTION: The aim of the present study was to examine the association between polymorphisms of interleukin 12 (IL-12) and rheumatoid arthritis (RA) associated biomarkers in a Chinese population. MATERIALS AND METHODS: We studied IL-12A rs2243115 T/G and IL-12B rs3212227 A/C polymorphisms in 615 RA patients and 839 controls in a Chinese population. Genotyping was done by a custom-by-design 48-Plex SNPscan™ Kit. The plasma level of IL-12 was measured by an enzyme-linked immune-sorbent assay in 90 RA patients and 90 controls. Clinical data with other potential diagnostic value were provided by the physicians. RESULTS: A significantly increased risk for RA associated with the IL-12A rs2243115 GG (GG versus TT: OR=4.81, 95% CI 1.33-17.36, P=0.017; and GG versus TG+TT: OR=4.55, 95% CI 1.27-16.36, P=0.020) genotype was evident among rheumatoid factor (RF) negative patients, and with the IL-12B rs3212227 AC (AC versus AA) and AC+CC (AC+CC versus AA) genotypes were evident among older patients (OR=1.48, 95% CI 1.06-2.06, P=0.020), RF positive patients (OR=1.35, 95% CI 1.04-1.75, P=0.026) and anti-cyclic citrullinated peptide antibodies (ACPA) negative patients (OR=1.53, 95% CI 1.11-2.10, P=0.009). The plasma level of IL-12 was significantly higher in RA patients (P<0.001). IL-12 plasma level of IL-12A rs2243115 TT (P<0.001) and IL-12B rs3212227 C allele (P<0.001) were significantly higher in RA patients than controls respectively. The plasma level of IL-12 of RF positive RA patients was significantly higher than RF negative patients (P=0.008), especially in rs3212227 AC patients (P=0.01). CONCLUSIONS: These findings suggested that the functional single nucleotide polymorphism (SNP) IL-12A rs2243115 GG genotype may increase the risk of RA in RF negative patients, and the IL-12B rs3212227 AC and AC+CC genotypes are associated with RA risk in older patients, RF positive patients and ACPA negative patients. The IL-12A rs2243115 T/G and IL-12B rs3212227 A/C allele might also impact the inflammatory reaction of IL-12 in patients with RA.
INTRODUCTION: The aim of the present study was to examine the association between polymorphisms of interleukin 12 (IL-12) and rheumatoid arthritis (RA) associated biomarkers in a Chinese population. MATERIALS AND METHODS: We studied IL-12Ars2243115 T/G and IL-12Brs3212227 A/C polymorphisms in 615 RApatients and 839 controls in a Chinese population. Genotyping was done by a custom-by-design 48-Plex SNPscan™ Kit. The plasma level of IL-12 was measured by an enzyme-linked immune-sorbent assay in 90 RApatients and 90 controls. Clinical data with other potential diagnostic value were provided by the physicians. RESULTS: A significantly increased risk for RA associated with the IL-12Ars2243115 GG (GG versus TT: OR=4.81, 95% CI 1.33-17.36, P=0.017; and GG versus TG+TT: OR=4.55, 95% CI 1.27-16.36, P=0.020) genotype was evident among rheumatoid factor (RF) negative patients, and with the IL-12Brs3212227 AC (AC versus AA) and AC+CC (AC+CC versus AA) genotypes were evident among older patients (OR=1.48, 95% CI 1.06-2.06, P=0.020), RF positive patients (OR=1.35, 95% CI 1.04-1.75, P=0.026) and anti-cyclic citrullinated peptide antibodies (ACPA) negative patients (OR=1.53, 95% CI 1.11-2.10, P=0.009). The plasma level of IL-12 was significantly higher in RApatients (P<0.001). IL-12 plasma level of IL-12Ars2243115 TT (P<0.001) and IL-12Brs3212227 C allele (P<0.001) were significantly higher in RApatients than controls respectively. The plasma level of IL-12 of RF positive RApatients was significantly higher than RF negative patients (P=0.008), especially in rs3212227 AC patients (P=0.01). CONCLUSIONS: These findings suggested that the functional single nucleotide polymorphism (SNP) IL-12Ars2243115 GG genotype may increase the risk of RA in RF negative patients, and the IL-12Brs3212227 AC and AC+CC genotypes are associated with RA risk in older patients, RF positive patients and ACPA negative patients. The IL-12Ars2243115 T/G and IL-12Brs3212227 A/C allele might also impact the inflammatory reaction of IL-12 in patients with RA.
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