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

Abstract

The protective immune response against Brucella involves T-cell-mediated immunity. T-lymphocyte receptors, CD28 and cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), bind the same ligands, CD80 (B7-1) and CD86 (B7-2) on antigen-presenting cells and regulate T cell activation. CD28 delivers stimulatory signals whereas CTLA-4 provides inhibitory signals for T cell activation. Here, we investigated the association of four polymorphisms in CTLA4 (þ49A/G [rs231775] and À318 C/T [rs5742909]) and its ligand CD86 (þ1057 G/A [rs1129055] and þ2379G/C [rs17281995]) with brucellosis infection. The study included 153 Iranian patients with active brucellosis and 128 healthy individuals as the control group. Genotyping of the CTLA4 and CD86 variants was performed using tetra amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) and PCRrestriction fragment length polymorphism analysis, respectively. It was found that the CTLA4 À318 CT genotype and T allele were present more frequently in cases than in controls and are therefore associated with an increased risk for brucellosis (À318 TT genotype; OR ¼ 2.544, P ¼ 0.002). Likewise, the CD86 þ1057 GA and AA genotypes and A allele were associated with an increased risk of brucellosis (þ1057 AA genotype; OR ¼ 3.81, P ¼ 0.001). However, no statistically significant difference between brucellosis patients and controls in the allele and genotype distributions of CTLA4, þ49A/G (P ¼ 0.859) and CD86, þ2379G/C (P ¼ 0.476) was found. In conclusion, CTLA4 À318 CT genotype and Tallele and the CD86 þ057 GA and AA genotypes and A allele play roles as risk factors for developing brucellosis infection in Iran.

“Like sugar in milk”: reconstructing the genetic history of the Parsi population

“…The frequency of this G allele is lower in the Iranians and Sindhi (0.60) and other South Asians (0.52) and East Asians (0.40). This polymorphism has been associated with the pathogenesis of pneumonia-induced sepsis and the G allele has been associated with a decreased risk of active brucellosis in Iranians [46]. The G variant has also been associated as an eQTL for decreased expression of IQBC1 , an IQ-motif-containing B1 gene that is highly expressed in Epstein–Barr virus-transformed B lymphocytes [47].…”

“Like Sugar in Milk”: Reconstructing the genetic history of the Parsi population

“…The frequency of this G allele is lower in the Iranians and Sindhi (0.60) and other South Asians (0.52) and East Asians (0.40). This polymorphism has been associated with the pathogenesis of pneumonia-induced sepsis and the G allele has been associated with a decreased risk of active brucellosis in Iranians (46). The G variant has also been associated as an eQTL for decreased expression of IQBC1, an IQ motif containing B1 gene that is highly expressed in EBV transformed B lymphocytes (45).…”

Relationship between CD14-159C/T gene polymorphism and acute brucellosis risk

“…Demographic characteristics of patients and their clinical complications are shown in Table 1. Brucellosis was diagnosed according to the clinical manifestations (including fever, night sweating, weakness, malaise, weight loss, splenomegaly, lymphadenophathy, myalgia and arthralgia) and positive blood cultures as described previously [29][30][31][32]. The control group included healthy blood donors with no evidence of brucellosis and genetic disorders and matched for age, sex, and geographic area.…”

“…Serological tests, defined as wright titre 1/160 plus mercaptoethanol test 1/ 80 or coomb's wright 1/320 certified the brucellosis infection. The complete details of the organism identification methods have been described previously in papers by this research team [29][30][31][32].…”