A non-synonymous single-nucleotide polymorphism in the gene encoding Toll-like Receptor 3 (TLR3) is associated with sero-negative Rheumatoid Arthritis (RA) in a Danish population.
BMC Res Notes. 2014 Oct 10;7(1):716
Authors: Laska MJ, Hansen B, Troldborg A, Lorenzen T, Stengaard-Pedersen K, Junker P, Nexø BA, Lindegaard HM
BACKGROUND: It has been suggested that polymorphisms in Toll-like Receptors (TLRs) are associated with Rheumatoid Arthritis (RA), but the implicated alleles have differed between studies. The aim of this investigation was to explore whether polymorphisms of TLR genes are associated with RA in a predominantly Caucasian population from Denmark using a case-control approach.
FINDINGS: DNA samples (3 university hospital outpatient clinics) were obtained from patients with RA (n = 704) and healthy controls (n = 639) in a Danish population. TLR single nucleotide polymorphisms (SNPs) were selected based on the previously reported associations with chronic autoimmune diseases. Genotyping for the TLR SNPs was performed using Sequenom Multiplex technology.We identified one SNP in TLR3, [(rs3775291, P = 0.02, OR (95% CI) 1.31 (1.1087-1.5493)] significantly associated with the whole RA cohort. Subgroup analysis according to IgM rheumatoid factor (RF) and anti-cyclic citrinullated peptide (CCP) status suggested a significant association of sero-negative RA with the rs3775291 A allele and disease activity in this subset.
CONCLUSION: These observations on a RA population of Danish ancestry suggest that variations in the TLR3 locus may be implicated in the pathogenesis of sero-negative RA. Since this TLR3 SNP has previously been associated with systemic lupus erythematous (SLE), the present findings support the notion that TLR3 genetic variants may represent a common risk factor in different chronic inflammatory conditions, including RA and SLE.
PMID: 25304972 [PubMed - as supplied by publisher]
Development and Validation of a 20K Single Nucleotide Polymorphism (SNP) Whole Genome Genotyping Array for Apple (Malus × domestica Borkh).
PLoS One. 2014;9(10):e110377
Authors: Bianco L, Cestaro A, Sargent DJ, Banchi E, Derdak S, Di Guardo M, Salvi S, Jansen J, Viola R, Gut I, Laurens F, Chagné D, Velasco R, van de Weg E, Troggio M
High-density SNP arrays for genome-wide assessment of allelic variation have made high resolution genetic characterization of crop germplasm feasible. A medium density array for apple, the IRSC 8K SNP array, has been successfully developed and used for screens of bi-parental populations. However, the number of robust and well-distributed markers contained on this array was not sufficient to perform genome-wide association analyses in wider germplasm sets, or Pedigree-Based Analysis at high precision, because of rapid decay of linkage disequilibrium. We describe the development of an Illumina Infinium array targeting 20K SNPs. The SNPs were predicted from re-sequencing data derived from the genomes of 13 Malus × domestica apple cultivars and one accession belonging to a crab apple species (M. micromalus). A pipeline for SNP selection was devised that avoided the pitfalls associated with the inclusion of paralogous sequence variants, supported the construction of robust multi-allelic SNP haploblocks and selected up to 11 entries within narrow genomic regions of ±5 kb, termed focal points (FPs). Broad genome coverage was attained by placing FPs at 1 cM intervals on a consensus genetic map, complementing them with FPs to enrich the ends of each of the chromosomes, and by bridging physical intervals greater than 400 Kbps. The selection also included ∼3.7K validated SNPs from the IRSC 8K array. The array has already been used in other studies where ∼15.8K SNP markers were mapped with an average of ∼6.8K SNPs per full-sib family. The newly developed array with its high density of polymorphic validated SNPs is expected to be of great utility for Pedigree-Based Analysis and Genomic Selection. It will also be a valuable tool to help dissect the genetic mechanisms controlling important fruit quality traits, and to aid the identification of marker-trait associations suitable for the application of Marker Assisted Selection in apple breeding programs.
PMID: 25303088 [PubMed - as supplied by publisher]
69The relationship between the 174G>C IL-6 gene polymorphism and ventricular arrhythmias in patients with ICD.
Europace. 2014 Oct;16 Suppl 3:iii26
Authors: Majewski JP, Senderek T, Lelakowski J
INTRODUCTION: There is an evidence indicating that inflammation may play a role in ventricular arrhythmia pathogenesis. IL-6 is a pleiotropic, proinflammatory cytokine which plays a role in the immune, the endocrine and the nervous system. We hypothesized that the polymorphism of the gene coding for IL-6 may be associated with the occurrence of ventricular arrhythmias.
METHODS: The study group consisted of 136 consecutive patients (pts) -117 males, mean age 59 y (21-88) in whom ICD was implanted as a primary (106 pts) or secondary (30 pts) prophylaxis of sudden cardiac death The pts were followed-up at 6 months intervals after implantation .Genotyping of the polymorphic locus 174 G>C in the promoter of the IL-6 gene was made by the polymerase chain reaction (PCR) with analysis of single nucleotide polymorphism (SNP). Serum levels of inflammatory markers including hsCRP, fibrinogen, IL-6, IL-18, IL-10, TNF-alpha, cd40L were obtained the day before implantation.
RESULTS: During the 24 months follow-up ventricular fibrillation (VF) occurred in 25 pts and ventricular tachycardia (VT) in 83 pts (sustained VT-25 pts, non-sustained VT-58 pts) In the study group 3 types of genotypes were detected in the polymorphic locus: GG, GC and CC. GC genotype was associated with higher incidence of VT and VF as compared to GG and CC genotypes (p=0.02). There was also a discordance of the genotype's distribution and the Hardy-Weinberg equilibrium. In pts without VT or VF GG and CC genotypes were more frequent than expected and GC genotype was less frequent than expected (p<0.05). There was no association between levels of inflammatory markers and the occurrence of VT or VF.
CONCLUSIONS: The 174 G>C polymorphism in the IL-6 gene may contribute to pathogenesis of ventricular arrhythmias.
PMID: 25298477 [PubMed - in process]
Genotyping the GALNT14 gene by joint analysis of two linked single nucleotide polymorphisms using liver tissues for clinical and geographical comparisons.
Oncol Lett. 2014 Nov;8(5):2215-2220
Authors: Liang KH, Yang PC, Yeh CT
A GALNT14 single nucleotide polymorphism, rs9679162, has recently been found to be capable of predicting chemotherapy responses in patients with far-advanced hepatocellular carcinoma (HCC). In the present study, a novel assay was designed and genotyping was performed on 244 surgically removed liver tissues. This assay employed two polymerase chain reaction (PCR)-generated restriction enzyme sites to simultaneously determine the genotypes of two adjacent single nucleotide polymorphisms (SNPs), rs9679162 and rs6752303, on the GALNT14 gene. Genotypes determined by this assay reached 100% concordance with those detected by the direct sequencing method. Clinical analysis showed that the TT genotype of rs9679162 was lower in percentage among patients with virus-originated HCC compared with those with non-viral HCC (22.57 vs. 47.06%, respectively; P=0.023). The proportion of the TT genotype in the 244 HCC patients (24.18%) did not deviate significantly from those of two public-domain (HapMap) Chinese cohorts from Denver, Colorado, USA (28.44%) and Beijing, China (30.15%) (P>0.05). The proportion of the TT genotype was significantly higher in Japanese and African populations (42.11-54.55%; P<0.0001) but significantly lower in an Italian cohort (7.84%; P=0.0004). In conclusion, the novel PCR-generated double restriction enzyme sites method could correctly determine the genotypes of two target SNPs in GALNT14 in liver tissues. The TT genotype was associated with the non-viral etiology of HCC. A marked variation in ethnicity was found for the distribution of this genotype.
PMID: 25295111 [PubMed - as supplied by publisher]