rs1805010

This pharmacogenetic study of 374 patients with metastatic renal cell carcinoma examined SNP associations with sunitinib-induced toxicity. The IL8 rs1126647 T allele was associated with increased hypertension risk (OR=1.69, P=0.024), and the IL13 rs1800925 T allele was associated with increased leukopenia (OR=6.76, P=0.020) and grade >2 toxicity (OR=1.75, P=0.028). No significant associations were found with progression-free survival, overall survival, or clinical response.

This study investigated the relationship between the IL4R rs1805010 (I50V) SNP and rheumatoid arthritis (RA) outcomes. RA patients homozygous for the minor allele (V50/V50) showed significantly higher Th17 cell frequencies, elevated IL-17 and IL-22 serum levels, higher clinical activity (DAS28), and accelerated radiographic progression with erosions at one year compared to I50/I50 or I50/V50 carriers, indicating the V50/V50 genotype impairs IL-4 inhibition of Th17 cell development.

This systematic literature review examines interleukin and interleukin receptor gene polymorphisms associated with rheumatoid arthritis (RA) pathogenesis, diagnostics, and treatment. The paper summarizes polymorphisms in multiple IL genes (IL-1B rs16944, rs1143634; IL-6 rs1800795, rs1800796; IL-10 rs1800896; IL-23R rs11209026; IL-17A rs2275913 and others) across diverse populations, their associations with RA susceptibility and disease severity, and discusses current and future immunologic therapeutic targets including TNF inhibitors and IL-6 receptor antagonists.

This systematic literature review examines interleukin (IL) and interleukin receptor gene polymorphisms associated with rheumatoid arthritis (RA), covering studies from the past 10 years. The review discusses the pathogenesis of RA as a multifactorial autoimmune disease where genetic factors account for approximately 60% of disease risk. Multiple polymorphisms across IL-1, IL-2, IL-4, IL-6, IL-8, IL-10, IL-15, IL-17, IL-18, and IL-23R genes have been investigated in various populations, with inconsistent results across populations. The paper also reviews current and future therapeutic targets including anti-TNF, anti-IL-1, anti-IL-6, and anti-IL-17 treatments.

This PhD thesis comprises four association studies examining inherited variations in inflammatory cytokine genes and their pathogenetic role in rheumatoid arthritis (RA), multiple myeloma (MM), and B-cell non-Hodgkin's lymphoma (B-NHL). Paper I found that CHI3L1 promoter polymorphisms (rs4950928) were significantly associated with serum YKL-40 concentrations in 238 RA patients (P < 2.0e-16) and 605 controls. Paper IV reported CHI3L1 rs4950928 associated with follicular lymphoma 10-year overall survival (HRCG = 2.04, 95% CI 1.17-3.54). Papers II and III examined gene-gene interactions in MM and B-NHL risk and prognosis.