Effect of Interleukin-10 -1082 A/G and Interleukin-12p40 1188 A/C Polymorphism on Susceptibility of Non- Hodgkin ’ s Lymphoma

Non-Hodgkin’s lymphomas (NHLs) are a diverse group of mature lymphoid neoplasms with a wide range of cellular, immunological, histological, and molecular heterogeneity. Numerous environmental and
genetic factors have been found to be associated with the incidence of these neoplasms; however the exact causes are beyond the current knowledge and there was inconclusive sole risk factor. as known to play a crucial role in the regulation of essential pathways. Blood  samples were collected from 55 confirmed patients with NHLs. Similar samples were collected from unrelated, age-matched 40 apparently healthy individuals to represent the control group. Informed consents from all participants were obtained which included age, gender, smoking status, diabetes mellitus presence, residence , first relative
family history of NHLs and body mass index. DNA was extracted from blood samples using ready purchased kit. Three sets of primer pairs were used to amplify IL-10, IL-12p40, and TLR2 (Toll-like receptor-2, as internal control) genes by using conventional PCR technique. Genotyping was performed by allele specific-PCR method. The levels of IL-10 and IL-12p40 in sera of NHLs patients and controls were  measured by using ready purchased ELISA kit.The polymorphism of IL-10 -1082A/G appeared in three genotypes: AA,AG and GG which represent 36.36%, 45.45% and 18.18%, respectively,among NHL patients compared to 32.5%, 35% and 32.5%%,respectively, in the control group. The differences between patients and control, however, were insignificant neither among genotypes nor at the allelic level.On the other hand, the SNP IL-12p401188A/C had three genotypes which were AA, AC and CC. These genotypes represented 32.73%, 38.18% and 29.09%, respectively, among NHL patients compared to 52.5%, 37.5% and 10%, respectively, among controls. There was a significant difference for the homozygous mutant genotype CC {OR (odd ratio) = 4.667, 95%CI (95% confidence interval) = 1.319 -16.512, P value = 0.017}. At allelic level, the mutant of C allele was more frequent among NHL patients (48.18%) than in controls (28.75%) with a highly significant difference (OR = 2. 304, 95%CI = 1.25-4.249, P = 0.007). The serum levels of IL-10 and IL-12p40 were significantly higher among NHL patients (458.31±241.126pg/ml and 156.44±54.188 pg/ml, P = 0.011 and 0.0001, respectively) than the control group (323.46±242.344 pg/ml and 107.34±56.957 pg/ml, respectively) as measured by an ELISA technique. The elevation of IL-10, although it was not significant, was associated with the AG genotypes. While the elevation of IL-12p40 was linked to CC genotypes. These data indicate that IL-10 SNP is not directly linked to the risk of NHLs. On the other hand, SNP in IL-12p40 showed such correlation and influenced by specific genotype.Seven other risk factor were studied. These are: age, family history, gender, body mass index (BMI), smoking, residency (urban vs rural), and type 2diabetes mellitus (DM-2). Out of these, four factors showed to be significantly associated with the risk of NHLs. These factors were gender (P= 0.009), body mass index (BMI) ( P=0.028), smoking (P= 0.005) and urban residence (P=0.007).
In conclusion, this study showed that IL-10-1082A/G polymorphism has no significant effect on either the risk of NHLs or serum levels of IL-10. In contrast, the allele C of the SNP IL-12p401188A/C could be
considered as a risk factor for NHLs.