Variation in cytokine genes can contribute to severity of acetabular osteolysis and risk for revision in patients with ABG 1 total hip arthroplasty: a genetic association study

<p>Abstract</p> <p>Background</p> <p>The differences in total hip arthroplasty (THA) survivorship may be influenced by individual susceptibility to periprosthetic osteolysis. This may be driven by functional polymorphisms in the genes for cytokines and cytokine receptors involved in the development of osteolysis in THA, thereby having an effect on the individual's phenotype.</p> <p>Methods</p> <p>We performed a study on 22 single-nucleotide polymorphisms (SNPs) for 11 cytokines and two cytokine receptor candidate genes for association with severity of acetabular osteolysis and risk to failure in THA. Samples from 205 unrelated Caucasian patients with cementless type THA (ABG 1) were investigated. Distribution of investigated SNP variants between the groups of mild and severe acetabular osteolysis was determined by univariate and multivariate analysis. Time-dependent output variables were analyzed by the Cox hazards model.</p> <p>Results</p> <p>Univariate analysis showed: 1) <it>TNF</it>-238*A allele was associated with severe osteolysis (odds ratio, OR = 6.59, <it>p </it>= 0.005, population attributable risk, PAR 5.2%); 2) carriers of the <it>IL6</it>-174*G allele were 2.5 times more prone to develop severe osteolysis than non-carriers (OR = 2.51, <it>p </it>= 0.007, PAR = 31.5%); 3) the carriage of <it>IL2</it>-330*G allele was associated with protection from severe osteolysis (OR = 0.55, <it>p </it>= 0.043). Based on logistic regression, the alleles <it>TNF</it>-238*A and <it>IL6</it>-174*G were independent predictors for the development of severe acetabular osteolysis. Carriers of <it>TNF</it>-238*A had increased cumulative hazard of THA failure according to Cox model (<it>p </it>= 0.024). In contrast, <it>IL2</it>-330*G allele predicted lower cumulative hazard of THA failure (<it>p </it>= 0.019).</p> <p>Conclusion</p> <p>Genetic variants of proinflammatory cytokines TNF-alpha and IL-6 confer susceptibility to severe OL. In this way, presence of the minor <it>TNF </it>allele could increase the cumulative risk of THA failure. Conversely, SNP in the <it>IL2 </it>gene may protect carriers from the above THA complications.</p

Association of FcγRIIa R131H polymorphism with idiopathic pulmonary fibrosis severity and progression

<p>Abstract</p> <p>Background</p> <p>A significant genetic component has been described for idiopathic pulmonary fibrosis (IPF). The R131H (rs1801274) polymorphism of the IgG receptor FcγRIIa determines receptor affinity for IgG subclasses and is associated with several chronic inflammatory diseases. We investigated whether this polymorphism is associated with IPF susceptibility or progression.</p> <p>Methods</p> <p>In a case-control study, we compared the distribution of FcγRIIa R131H genotypes in 142 patients with IPF and in 218 controls using allele-specific PCR amplification.</p> <p>Results</p> <p>No differences in the frequency of FcγRIIa genotypes were evident between IPF patients and control subjects. However, significantly impaired pulmonary function at diagnosis was observed in HH compared to RR homozygotes, with evidence of more severe restriction (reduced forced vital capacity (FVC)) and lower diffusing capacity for carbon monoxide (D<smcaps>L</smcaps>_CO). Similarly, increased frequency of the H131 allele was observed in patients with severe disease (D<smcaps>L</smcaps>_CO< 40% predicted) (0.53 vs. 0.38; p = 0.03). Furthermore, the H131 allele was associated with progressive pulmonary fibrosis as determined by > 10% drop in FVC and/or > 15% fall in D<smcaps>L</smcaps>_COat 12 months after baseline (0.48 vs. 0.33; p = 0.023).</p> <p>Conclusions</p> <p>These findings support an association between the FcγRIIa R131H polymorphism and IPF severity and progression, supporting the involvement of immunological mechanisms in IPF pathogenesis.</p

Pesticide Residues

METHODOLOGY for residue analysis has advanced rapidly during the current review period, from November 1962 through October 1964. Notable progress has been made in the development and refinement of methods of analysis by which any or all of a large number of pesticide residue chemicals can be detected and measured in one general operation. This is of particular significance because great interest has developed-outside the scientific community as well as within - in the possible presence of pesticide chemicals in all parts of our environment, including man himself. Only by the use of improved methodology will it be possible to accomplish the task of detecting, identifying, and measuring the many possible residual pesticide chemicals. It is only after the presence or absence of these chemicals in any part of our environment has been proved unequivocally that the medical man, the lawyer, the lawmaker, the administrators in government and in industry, and other interested groups can assess the significance of such residues. There are 300 to 400 chemicals registered for use on food products alone, and a few hundred more are registered for other uses whereby they may become part of our environment. The chemist cannot know which of the hundreds of possible pesticide chemical residues to look for in samples of air, water, soil, plants, human and animal tissues, prepared foods, etc. There is an urgent need for general procedures that can identify and measure a large number of chemicals at one time. They must be highly sensitive and accurate, since it is essential that all monitoring of our environment be at a level considerably below any tolerance or otherwise critical level, so that trends can be more readily recognized and assessed for significance. Upward or downward trends in any portion of our environment will be recognizable only when the methodology becomes sufficiently sensitive and accurate so that analyses in the fraction-of-a-part-per-million or even part-per-billion range become routinely dependable (Fischbach, H. Pub. 1082, National Research Council, p. 55, Nov. 29,1962)