IL-10 G-1082A Research Articles

Investigation of genes coding for inflammatory components in Parkinson's disease

Several findings obtained recently indicate that inflammation may contribute to the pathogenesis in Parkinson's disease (PD). Genetic variants of genes coding for components involved in immune reactions in the brain might therefore influence the risk of developing PD or the age of disease onset. Five single nucleotide polymorphisms (SNPs) in the genes coding for interferon-gamma (IFN-gamma; T874A in intron 1), interferon-gamma receptor 2 (IFN-gamma R2; Gln64Arg), interleukin-10 (IL-10; G1082A in the promoter region), platelet-activating factor acetylhydrolase (PAF-AH; Val379Ala), and intercellular adhesion molecule 1 (ICAM-1; Lys469Glu) were genotyped, using pyrosequencing, in 265 patients with PD and 308 controls. None of the investigated SNPs was found to be associated with PD; however, the G1082A polymorphism in the IL-10 gene promoter was found to be related to the age of disease onset. Linear regression showed a significantly earlier onset with more A-alleles (P = 0.0095; after Bonferroni correction, P = 0.048), resulting in a 5-year delayed age of onset of the disease for individuals having two G-alleles compared with individuals having two A-alleles. The results indicate that the IL-10 G1082A SNP could possibly be related to the age of onset of PD.

Composite risk assessment of cervical cancer and precancer by learning algorism of single nucleotide polymorphisms and HPV genotypes

9713 Background: While multiple environmental and host factors are involved in cancer development, the carcinogenesis of uterine cervix stand for a relatively simplified model to unveil the complex city, by the fact that virtually all cervical cancers are related to HPV. However, genetic susceptibilities of host response to viral infection and oncogenesis also play important roles. Previously, we have dissected the relative risks of individual viral genotype and host single nucleotide polymorphisms (SNP) in cervical cancer development (Int J Cancer, 1999; Gyn Oncol, 2001; Int J Cancer, 2003). However, gene-gene and gene-environmental interactions must be taken into account before the global risk assessment can be realized. Methods: Three HPV genotype groups (type 16, 18 and 58) and 11 SNP (MCP1 G2518A, IL10 G592T, IL10 C819T, IL10 G1082A, P53 R72P, IL4 C590T, IL4 C34T, MMP1 G1607GG, FAS A670T, IL4RA C3223T and IL12B A1188C) were analyzed in a cohort of 92 high grade squamous intraepithelial lesion (HSIL), 135 squamous cell carcinoma (SCC) of uterine cervix, and 70 normal controls. The Bayesian probabilistic network was generated to classify the degrees of relationship of the biomarkers toward the diagnosis. A decision tree was defined by the key biomarkers was then computed by using the J48 learning algorism. Results: The J48 algorithm gave an overall sensitivity of 60.3%, specificity of 77.7%, PPV of 56.8% and F measure of 58.5%. A decision tree with a hierarchy order of HPV group, MMP1, IL4RA/P53 and IL12B/MCP1 polymorphisms was generated. As shown in the table, this model more accurately predicted normal and SCC than HSIL. Conclusions: This study showed a promising feasibility of assessing cervical cancer risk by multiple host SNP and HPV genotypes. No significant financial relationships to disclose.