No abstract

Crimean-Congo hemorrhagic fever (CCHF) is a viral zoonosis. Toll-like receptors (TLRs) initiate signaling cascades leading to the activation of the innate immune system following CCHF infection. In this study, TLR7 (Gln11Leu, c.4-151A/G, and +1817G/T) polymorphisms were investigated in CCHF patients using polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP). The study population comprised 149 CCHF patients and 171 controls. For the TLR7 Gln11Leu polymorphism, there was no significant difference between the case and control groups in allele (P = 0.144) and genotype frequencies (P = 0.219). In the TLR7 IVS1 +1817G/T polymorphism, a statistically significant difference was found in allele frequencies (P = 0.026), but there was no significant difference in the TLR7 c.4-151A/G polymorphism (P = 0.310). There was a statistically significant difference in the distribution of the TLR7 c.4-151GG genotypes frequencies between patients and controls (P = 0.042; OR = 2.23). Furthermore, there were statistically significant associations between the TLR7 c.4-151A/G polymorphism and both severe disease and patient mortality (P < 0.001 and P = 0.047, respectively). The TLR7 IVS1 +1817TT genotype was also significantly associated with the case group but not the control group (P = 0.045). A strong positive linkage among TLR 7 variants was found using haplotype analysis. The incidence of two haplotypes, AGG and AGT, was determined to exhibit significant differences between the case and control groups (P < 0.001 and P < 0.001, respectively). These findings suggest that the TLR7 IVS1 +1817G/T and TLR7 c.4-151A/G polymorphisms may be important in the susceptibility or clinical course of CCHF disease.

Crimean-Congo hemorrhagic fever (CCHF) is an infectious disease that is caused by CCHF virus. A family of transmembrane receptors called as Toll-like receptors (TLRs) selectively acts in recognizing a wide range of microbial components and endogenous molecules released by damaged tissue and have been preserved throughout evolution. TLRs initiate some signaling cascades which activate the innate immune system. Mainly four TLRs act in protection against viral infections; TLR3 is one of them. TLR3 identifies dsRNA. By producing inflammatory cytokines and type I interferons, it generates an antiviral immune response. Proper response to TLR ligands may be impaired by single nucleotide polymorphisms (SNPs) within TLR genes in some indviduals, and this can cause varied susceptibility to infections. In the present work, polymerase chain reaction-based restriction fragment length polymorphism is used to analyze the frequencies of TLR3 (c.1377C/T and -7C/A) polymorphisms in 149 CCHF patients and 171 healthy adults as controls, in Cumhuriyet University, Sivas/Turkey. We also investigated the relation between these polymorphisms and severity or mortality of CCHF disease. This is the first study investigating the TLR3 SNPs in patients with CCHF. In the present study, the frequency of the TLR3 (c.1377C/T and -7A/C) genotypes in fatal and non-fatal cases were comparable, however, the homozygous mutant (TT) genotype frequency of TLR3 c.1377C/T in CCHF patients was significantly higher than that of the healthy controls. In conclusion, presence of TLR3 c.1377 TT genotype may have a role in the susceptibility to CCHF. J. Med. Virol. 88:1690-1696, 2016. © 2016 Wiley Periodicals, Inc.

Abstract. Matrix metalloproteinase (MMP)-3 and MMP-9 polymorphisms are characterized by plaque stability in coronary arteries. The aim of the current study was to investigate the 5A/6A polymorphism in the MMP-3 gene and C/T polymorphism in the MMP-9 gene in patients with coronary artery disease (CAD). The study population consisted of 400 patients who underwent coronary angiography. There were two groups consisting of 200 consecutive patients with CAD, presenting with stable angina pectoris, and 200 consecutive patients exhibiting normal coronary arteries. Two single nucleotide polymorphisms in the MMP gene, MMP-3 and MMP-9, were detected using a polymerase chain reaction-restriction fragment length polymorphism assay. Mean age, gender distribution, smoking status, presence of diabetes mellitus and hypercholesterolemia were identified to be similar between the groups. One hundred and twenty seven (63.5%) patients had hypertension in the CAD group, whereas only 55 (27.5%) patients had hypertension in the control group (P<0.001). No significant difference in frequency of alleles and genotypes of MMP-9 C→T between the CAD and control groups was identified. The 5A allele frequency of MMP-3 in the CAD group was significantly higher when compared with the control group (P<0.001; odds ratio=2.18). The genotype frequency of MMP-3 5A/5A in the CAD group was significantly higher when compared with the controls (P=0.005). When compared with the homozygous wild-type (6A/6A) genotype of the MMP-3 gene, the cumulative frequency of heterozygote and homozygote genotypes of the MMP-3 gene was significantly higher in the CAD compared with the control group (P<0.001).Thus, the present study demonstrated that the 5A/5A and 6A/5A+5A/5A genotypes of the MMP-3 gene were associated with an increased risk of CAD.

Crimean Congo hemorrhagic fever (CCHF) is a tick-borne disease caused by the Crimean Congo hemorrhagic fever virus (CCHFV). Toll-like receptors (TLRs) are type 1 transmembrane proteins of immune cells that play a critical role in innate and adaptive immunity. The present study first time aims to investigate the relation between TLR10 gene polymorphisms (720A/C, 992T/A, and 2322A/G), severity/non-severity, fatality/ non-fatality, and CCFH disease by using PCR-RFLP assay in a Turkish population.TLR10 720A/C polymorphism was determined to be statistically significant both genotype and allele frequency (P = 0,011, P = 0.015, respectively). TLR10 992T/A polymorphism was found statistically significant relationships between patient and control (P = 0.026) and individual with AA genotype have approximately three times greater risk than TT genotype (OR = 2.93). There was not a significant difference in 2322A/G genotype distribution (P = 0.152). There were also statistically significant associations between both TLR10 992T/A and 2322A/G polymorphism and patient mortality (P = 0.001 and P = 0.008, respectively). We have not found statistically any linkage among TLR10 haplotype, but individual AAA and GAT haplotype have higher risk than individual AAT haplotype (OR = 3.22, OR = 1.93, respectively). Consequently, this study shows that pathogenesis of CCHF disease is associated with the TLR10 720A/C and 992T/A polymorphisms. There is a statistically significant association in fatal/non-fatal patients with TLR10 720A/C and 992T/A. The TLR10 992AA genotype might increase and TLR10 720CC genotype might decrease susceptibility to pathogenesis of CCHF disease. TLR 10 polymorphisms may be also an important biomarker for CCHF susceptibility and fatality rate. K E Y W O R D SCrimean-Congo hemorrhagic fever virus, genetic polymorphism, TLR10