A genetic association study of the CLEC12A gene in rheumatoid arthritis

ObjectiveThe CLEC12A gene codes for an immune inhibitory receptor that maps to 12p13.2. Since an increase in CLEC12A mRNA correlates with rheumatoid factor values greater than 40 IU/ml in rheumatoid fibroblast-like synovial cells, this study assessed the potential of an association between CLEC12A and rheumatoid arthritis (RA) using a phenotype-based approach.MethodsA discovery cohort of Western European ethnicity was genotyped for eight tag single nucleotide polymorphisms. Statistical analyses relied on the transmission disequilibrium test, relative risk and 95% confidence interval (CI) calculations. Observed haplotype frequencies were compared to expected frequencies using a family-based association test. Statistically significant associations were further tested in a second cohort of unrelated West-European RA patients.ResultsAn overtransmission of the C allele of the rs1323461 tag single nucleotide polymorphism was observed (56.6% of allele C transmission, P = 0.046) in the discovery cohort. The relative risk of the AC and CC genotypes when compared to the AA genotype was high (relative risk = 4.08; 95% CI: 1.52–10.95, uncorrected P = 2.1 × 10^?3), particularly in the subgroup of erosive RA (relative risk = 5.27; 95% CI: 1.53–18.19, uncorrected P = 2.1 × 10^?3), both remaining statistically significant after conservative Bonferroni's correction. The CGAGCCGA haplotype was observed more frequently than expected (P = 0.013). In the second cohort, the C allele had a tendency to be more frequent in RA patients (82.4%) than controls (79.2%) (P = 0.069).ConclusionWe report a potential genetic association of CLEC12A with RA. Since CLEC12A encodes for the myeloid inhibitory C-type lectin-like receptor that modulates cytokine synthesis, this receptor may contribute to the pathogenesis of RA.     

Mercury and methylmercury concentrations in Mediterranean seafood and surface sediments, intake evaluation and risk for consumers

Total mercury and methylmercury concentrations were measured in sediments and marine organisms from the Taranto Gulf to understand their distribution and partitioning. Sediment concentrations ranged from 0.036 to 7.730 mg/kg (mean: 2.777 mg/kg d.w.) and from 1 to 40 μg/kg (mean: 11 μg/kg d.w.) for total mercury (THg) and methylmercury (Me-Hg), respectively. In mollusks THg ranged from n.d. to 1870 μg/kg d.w. while in fish from 324 to 1740 μg/kg d.w. Me-Hg concentrations in fish ranged from 190 to 1040 μg/kg d.w. and from n.d. to 1321 μg/kg d.w. in mollusks. THg exceeded the maximum level fixed by the European Commission (0.5 mg/kg w.w.) only in gastropod Hexaplex t. The calculated weekly intake was in many cases over the Provisional Tolerable Weekly Intake established by EFSA for all edible species. These results seem to indicate that dietary consumption of this seafood implicates an appreciable risk for human health.     

The predominance of type I oligosaccharides is a feature specific to human breast milk

Human milk and colostrum contain ～12-13 g/L and ～22-24 g/L of oligosaccharides, respectively. The chemical structures of >100 human milk oligosaccharides (HMO) have been characterized to date. We determined the concentrations of 10 neutral and 9 acidic colostrum HMO collected during the first 3 d of lactation by using reverse phase HPLC after derivatization with 2-aminopyridine or 1-methyl-3-phenyl-5-pyrazolon. The predominant oligosaccharides were Fuc(α1-2)Gal(β1-4Glc (2'-FL), Fuc(α1-2)Gal(β1-3)GlcNAc(β1-3)Gal(β1-4)Glc (LNFP I), Fuc(α1-2)Gal(β1-3)[Fuc(α1-4)]GlcNAc(β1-3)Gal(β1-4)Glc (LNDFH I), and Gal(β1-3)GlcNAc(β1-3)Gal(β1-4)Glc (LNT), the concentration of each of which was ～1-3 g/L. Because these HMO, other than 2'-FL, all contain the Lacto-N-biose type I structure [Gal(β1-3)GlcNAc], we conclude that HMO containing the type I structure predominate over those containing the N-acetyllactosamine type II structure [Gal(β1-4)GlcNAc]. This appears to be a feature that is specific to humans, because the milk and colostrum of other species, including apes and monkeys, either contain only type II oligosaccharides or type II predominate over type I. It is possible that type I HMO may have importance as substrates for beneficial bifidobacteria in breast-fed infants. The biological importance of type I HMO predominance warrants further study, both in relation to human health and to human evolution.