Is Elevated Serum IL-10 in B-CLL Associated with IL-10 Promoter Polymorphisms?.

Interleukin-10 (IL-10), a cytokine that regulates inflammation, may play an important role in B-cell chronic lymphocytic leukemia (B-CLL), because of the reported association of high serum IL-10 levels with a lower prognosis of survival. Using the Bio-Plex protein array system, we confirmed that B-CLL patients exhibit higher median IL-10 levels (3.54 pg/ml, n=50) as compared to controls (1.28 pg/ml, n=33) (p<0.0001). We are in the midst of determining B-CLL V_H gene mutation status and IL-10 levels. To determine if elevated IL-10 levels are due to inherent genetic polymorphisms, we examined three single nucleotide polymorphisms (SNPs) in the proximal end of the promoter region of the IL-10 gene (-1082 A/G, −819 T/C, and −592 A/C) that may affect IL-10 transcription levels. DNA from an overlapping set of 54 B-CLL patients and 48 normals was genotyped using the Transgenomic WAVE system. The difference in allele frequencies at a single locus showed no trend towards significance between groups using the Pearsons chi-square test and Odds Ratios (OR) with 95% Confidence Intervals (CI) for each SNP (-1082 (p = 0.686, OR = 1.122, CI = 0.641–1.966), −819 (p = 0.844, OR = 1.062, CI = 0.585–1.926) and −592 (p = 0.720, OR = 1.116, CI = 0.613–2.031)). B-CLL cases and normal subjects showed no significant departure from Hardy-Weinberg equilibrium in single locus genotype frequencies. Differences in single locus genotype frequencies between B-CLL cases and controls showed no significant differences for each SNP (−1082 (p = 0.600, OR = 1.366, CI = 0.425–4.389), −819 (p = 0.638, OR = 0.727, CI = 0.192–2.749), and −592 (p = 0.638, OR = 0.727, CI = 0.192–2.749)). The haplotype frequencies were calculated using maximum likelihood method based on the observed genotypes. The differences in maximum likelihood haplotype frequencies, between the B-CLL cases and controls, were insignificant (p = 0.754). The haplotype pair genotype frequency differences between the B-CLL cases and controls were also insignificant (p = 0.921). In conclusion, the allele, genotype, and haplotype frequencies of IL-10 SNPs −1082, −819, and −592 show no trend towards significance overall. This suggests that these promoter SNPs do not contribute to elevated serum IL-10 in B-CLL. However, a suggestion of association with V_H gene mutation status is being further investigated with a larger sample size.