Toll-like receptor-9 gene polymorphism in common variable immunodeficiency.

Common variable immunodefi ciency (CVID) is a primary immunodeficiency involving a heterogeneous group of disorders characterized by recurrent bacterial infections and defi cient production of different classes of antibodies. The predisposing genetic factors associated with CVID remain unknown [1], although homozygous defects in ICOS or CD19 have been detected in a very small number of patients [2,3]. Toll-like receptors (TLRs), one of the tools of the innate immune system, are involved in initiating signaling pathways of immune and infl ammatory genes. TLR9, which recognizes unmethylated CpG-DNA sequences, is expressed at high levels in B cells. TLR9 signaling via CpG-DNA sequences plays a direct role in initiating and sustaining humoral immunity as well as memory B cell responses [4,5]. Recent studies have revealed broad TLR9 defects in CVID consisting of both a lack of TLR9 expression and defective TLR9 function in B cells [6]. Twenty single nucleotide polymorphisms (SNPs) have been identifi ed in CVID. To evaluate the candidacy of TLR9 as a CVID susceptibility gene in the Turkish population, we investigated the association between the TLR9 -1237T/C promoter polymorphism and CVID. Our study included 30 CVID patients and 29 age-matched healthy controls. The study was approved by the medical ethics committee of Uludag University and informed consent was obtained from all patients and/or their parents or guardians. Genomic DNA was obtained from peripheral blood leukocytes. We genotyped the TLR9-1237T/C promoter polymorphism using polymerase chain reaction-restriction fragment length polymorphism analysis. Genomic DNAs were amplifi ed by 5′-CCTGCTTGCAGTTGACTGTG-3′(forward primer) and 5′-CCCTGTTGAGAGGGTGACAT-3′ (reverse primer), followed by BstNI restriction enzyme (5 U/μL; Genemark) digestion [7]. There were no signifi cant differences between patient and control groups in terms of age or sex. Analysis of TLR9 gene polymorphisms showed that 9 CVID patients (30%) and 6 healthy controls (20%) had the TC genotype. The TT genotype (wild-type) was detected in 21 CVID patients and 23 controls. None of the individuals included in the study displayed the CC genotype (Figure).