CTLA-4 and CD86 genetic variants and haplotypes in patients with rheumatoid arthritis in southeastern China

Abstract

ABSTRACT. The cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and costimulatory molecule (CD80/CD86) genes are important susceptibility genes associated with autoimmune diseases. CTLA-4 polymorphisms have been found to be associated with various autoimmune diseases. However, the association data are inconsistent for rheumatoid arthritis (RA). We investigated the genetic association of CTLA-4 and CD86 polymorphisms with RA in a Chinese population. Four single nucleotide polymorphisms (SNPs) (rs5742909 and rs231775 in CTLA-4, and rs17281995 and rs1129055 in CD86) were genotyped in 213 patients with RA and 303 healthy controls using polymerase chain reaction-restriction fragment length polymorphism. The genotype and allele distributions of rs5742909 differ significantly between RA patients and controls (P < 0.05) and the dominant model was found to be the best inheritance model. Stratification studies showed that CTLA-4 gene polymorphisms were more significantly associated with rheumatoid factor-negative and anti-cyclic citrullinated peptide-negative subgroups in the southeastern Han Chinese population. We also found that the haplotype of 2 CTLA-4 SNPs showed significant association with the disease (P = 0.0025) with the T-A (OR = 1.88, 95%CI = 1.12-3.15) and T-G (OR = 3.45, 95%CI = 1.10-10.87) haplotypes being observed more frequently in cases than in controls. We failed to find any significant association of the 2 CD86 SNPs with RA. These results indicate that the polymorphisms of CTLA-4 (rs5742909) may be important genetic factors for RA risk in the southeastern Han Chinese population.

Investigation of CTLA‐4 and CD86 gene polymorphisms in Iranian patients with brucellosis infection

“…On the other hand, our study failed to show any association between CTLA4 + 49 A/G and CD86 +2379G/C variants and brucellosis risk. In agreement with our findings, these SNPs have not been associated with risk of COPD , RA , or systemic sclerosis . However, these polymorphisms have been shown to be associated with primary biliary cirrhosis and hepatitis B infection .…”

The effect of CTLA-4 A49G polymorphism on rheumatoid arthritis risk: a meta-analysis

“…Among which, 16 studies were irrelevant. At last, a total of 27 eligible independent case–control studies in 24 articles were included [9-33]. The characteristics of selected studies are summarized in Table 1.…”

Association between the CTLA-4, CD226, FAS polymorphisms and rheumatoid arthritis susceptibility: A meta-analysis

“…Four articles were excluded because 2 were review articles, 1 contained duplicate data, and 1 had no data concerning the polymorphisms. Thus, 19 studies met our inclusion criteria [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31]. They consisted of 8 studies on the CTLA-4 polymorphism with 2093 patients and 2480 controls, 5 on the CD226 polymorphism with 2278 patients and 1940 controls, 6 on the FAS polymorphism with 546 patients and 618 controls, and 3 on the FASL polymorphism with 321 patients and 307 controls (Fig.…”

“…While some studies have found that CTLA-4 rs5742909, CD226 rs763361, FAS-670 rs1800682, and FASL rs763110 polymorphisms are associated with RA, other studies have reported no such association [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31]. To overcome the limitations of individual studies, resolve inconsistencies, and reduce the likelihood that random errors are responsible for false positive or false negative associations [32][33][34], we performed a meta-analysis to determine whether these polymorphisms are associated with RA susceptibility.…”