Association of Dectin-1 and DC-SIGN gene single nucleotide polymorphisms with fungal keratitis in the northern Han Chinese population.

PURPOSE: Dendritic cell-associated C-type lectin-1 (Dectin-1) and dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) play a crucial role in the early procedure of fungal pathogen defenses. The present study evaluated the associations between Dectin-1 and DC-SIGN gene single nucleotide polymorphisms (SNPs) and susceptibility to fungal keratitis (FK) in the northern Han Chinese population. METHODS: The polymorphisms of Dectin-1 (rs17206002, rs3901533, rs11053613, and rs3901532) and DC-SIGN (rs4804803, rs2287886, rs735239, and rs735240) for 109 FK patients and 220 matched healthy controls were determined by PCR and DNA direct sequencing assay. RESULTS: Each SNP was consistent with Hardy-Weinberg equilibrium (p>0.05). The frequencies of genotypes and alleles for rs735239 and rs735240 (DC-SIGN) showed statistical differences between patients and control groups (p<0.05). The wild G allele of rs735239 and the wild A allele of rs735240 were significantly higher in patients (p=0.003, OR=1.766, 95% confidence interval [CI] 1.207-2.585; p=0.014, OR=1.609, 95% CI 1.100-2.355, respectively). No association with a risk of FK was found for the remaining SNPs (p>0.05) even after ruling out clinical characteristics, such as severity degree and case history. Carriers of the haplotype TC (rs4804803 and rs2287886) had a higher risk of developing fungal keratitis (p=0.007, OR=1.710, 95% CI 1.154-2.534). The distribution of haplotypes AG and GA (rs735239 and rs735240) between the two groups also showed significant differences (p=0.014, p=0.003, respectively). CONCLUSIONS: Two SNPs of DC-SIGN (rs735239 and rs735240) are associated with susceptibility to FK in the northern Han Chinese population. The haplotypes of DC-SIGN may be susceptible to the risk of FK, whereas the analysis of Dectin-1 gene polymorphisms showed no significant association with FK risk. Further research with a larger sample is recommended.

Association of TLR2 and TLR4 gene single nucleotide polymorphisms with Fungal Keratitis in Chinese Han population.

PURPOSE: Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4) play a crucial role in the primary defense against fungal pathogens, and since genetic variation in genes may regulate the response. This study aimed to test whether variants in the TLR4 gene are associated with fungal keratitis (FK) of Chinese Han population. MATERIALS AND METHODS: Two-hundred sixty-nine subjects (109 cases and 160 matched controls) in a Han Chinese population were genotyped. Seven single nucleotide polymorphisms (SNPs) which located, respectively, in the TLR2 and TLR4 genes were selected and their associations with FK risk factors were assessed. RESULTS: Allele A of TLR4 rs10983755 was found significantly higher in the group of FK patients, being detected in 32.11% of the FK patients alleles and in 22.19% of the healthy control alleles (p = 0.01).Those AA/AG genotypes carrying the allele A of rs10983755 had a risk effect on the etiology of FK, and the odds ratio for the FK patients versus controls was 2.075 (OR = 2.075, 95%CI = 1.264-3.407). The Ht3 haplotype, which carried the A allele of TLR4 rs10983755, was associated with the significantly increased risk of FK (OR = 1.786, 95%CI = 1.207-2.642). While, the Ht2 haplotype, which carried the wild G allele of TLR4 rs10983755, was a protective haplotype (OR = 0.488, 95%CI = 0.333-0.715). The genotype and allele frequency of TLR2 showed no differences between the two groups (p > 0.05). CONCLUSIONS: The rs10983755, located in the 5'-untranslated region (UTR) of TLR4, was most strongly associated with FK of Chinese Han population (p < 0.05). The analysis of TLR2 gene polymorphisms showed no significant association upon FK susceptibilities of Chinese Han population.

Invasive fungal infections in patients with systemic lupus erythematosus: experience from affiliated hospitals of Catholic University of Korea.

The purpose of study was to determine the nature, outcomes and associated risk factors of invasive fungal infection (IFI) in patients with systemic lupus erythematosus (SLE), and compare the incidence of IFI in patients with rheumatoid arthritis (RA). A total of 1155 patients with SLE and 2004 patients with RA were retrospectively reviewed between 1992 and 2007. Twelve cases of IFI patients were identified in SLE patients (6 Aspergillus spp.; 5 Cryptococcus spp.; 1 Candida spp.). The incidence of IFI was significantly higher in patients with SLE than RA (1.04 vs. 0.15%). Among 12 patients with SLE, 10 had high Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores (>or=8). The most commonly involved organ was the lung (n = 6), followed by the meninges (n = 4). Most of SLE patients with IFI (91.7%) had taken steroids prior to IFI. Three SLE patients resulted in death. Notably, these patients were all infected with Aspergillus spp. The mortality was associated with the presence of leukopenia, high anti-DNA antibodies and high SLEDAI. Collectively, IFI is more common in patients with SLE than in patients with RA. High disease activity in patients with SLE might contribute to increased risk of IFI. In addition, mortality was associated with aspergillus infection, leukopenia and high anti-DNA antibodies.