rs4073

This case-control study of 170 Tunisian asthmatic children and 170 healthy controls found significantly elevated IL-8 serum and mRNA levels in asthmatic children, particularly those with moderate-to-severe disease. IL-8 gene variants rs4073 (A/T) and rs2227306 (C/T) were significantly associated with increased childhood asthma risk (OR=1.78, P=0.0005 and OR=1.42, P=0.040, respectively), with rs4073 T allele conferring higher risk for asthma severity.

This prospective case-control study examined genetic variation in immune response genes and prostate cancer risk in the Prostate Cancer Prevention Trial (PCPT) placebo arm. Among 881 cases and 848 controls, the minor allele of rs3212227 in IL12(p40) was associated with increased prostate cancer risk (OR=1.30, 95% CI 1.10-1.53, P-trend=0.0017), particularly for lower-grade disease. The minor alleles of IL10 tagSNPs rs3021094 (OR=1.31, 95% CI 1.03-1.66, P-trend=0.03) and rs1800890 (OR=0.87, 95% CI 0.75-0.99, P-trend=0.04) showed significant associations. The study investigated whether observed associations were explained by PSA-associated detection bias and found that associations persisted in men with low PSA levels.

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.

A prospective study of 568 Chinese non-small-cell lung cancer (NSCLC) patients found that four immune gene polymorphisms were independently associated with survival: IL-5R rs11713419 (5'-UTR, P=0.001), IL23R rs6682925 (5'-FR, P=0.017), TLR1 rs5743551 (5'-FR, P=0.02), and TLR3 rs3775291 (Leu412Phe, P=0.01). Patients carrying 1 unfavorable locus had 124% increased mortality risk (HR=2.24, 95% CI: 1.33-3.75), and those with 2-4 unfavorable loci had 175% increased risk (HR=2.75, 95% CI: 1.67-4.51). Combined SNP and clinical risk score model achieved 5-year AUC of 0.831 versus 0.484 for clinical factors alone.

Nested case-control study of 258 prostate cancer cases and 258 matched controls in the CLUE II prospective cohort examining genetic variants in inflammation and obesity-related genes. The IL10 -1082G>A variant (rs1800896, A allele) was positively associated with prostate cancer risk (AG vs GG: OR=1.69, 95% CI 1.10-2.60; AA vs GG: OR=1.81, 95% CI 1.11-2.96), while a TLR4 variant (rs4986790) showed inverse association, and no consistent associations were found for obesity-related gene variants.

A case-control association study testing the IL-8 gene polymorphism at position -251 (rs4073) in 219 VUR patients and 292 controls found no significant differences in genotype frequency between cases and controls, nor between patients with and without renal parenchymal scarring. The study concludes that IL-8 gene polymorphism is not involved in the pathogenesis of familial vesico-ureteral reflux.

This review discusses modifier genes (additional genetic factors) that influence the severity and presentation of monogenic disorders. The paper identifies and summarizes modifier genes for three common autosomal recessive diseases: spinal muscular atrophy (SMA, with modifiers SMN2, PLS3, ZPR1), familial Mediterranean fever (FMF, with modifiers MICA and SAA1), and cystic fibrosis (CF, with modifiers MBL2, TGFβ1, IFRD1, IL-8, and EDNRA). These findings demonstrate that genotype does not always predict phenotype, and explain variability in disease severity through gene-gene interactions.