Functional multigenic variations associated with hodgkin lymphoma

Abstract

Introduction: The current study aimed to describe genotypes associated with Hodgkin lymphoma (HL) in a cohort of Saudi and non-Saudi patients and discuss their possible susceptibility to HL. Methods: We studied clinical, histopathological, and laboratory findings of HL patients admitted over 12 years duration, at King Fahd University Hospital, KSA. The genomic DNAs of HL patients (n = 61) and normal control subjects (n = 36) were extracted, and genotyping was performed using the Illumina human exome bead chip. Set of HL patients and set of normal controls were included in this study. Results: A total of 35 DNA variants were found to be highly significant with the P-value <9.90 × 10−11 among 243 345 exonic biomarkers and obeying the Hardy-Weinberg equilibrium. Nine, MEGF11-rs150945752 (P-value 1.20 × 10−12), CACNA1I- s58055559 (P-value 1.93 × 10−12), DECR2-rs146760080 (P-value 2.19 × 10−12), STAB1-rs143894786 (P-value 2.45 × 10−12), ZNF526-rs144433879 (P-value 2.76 × 10−12), CPLANE1-rs200612080 (P-value 3.77 × 10−12), DLK1-rs1058009 (P-value 5.95 × 10−12), RTN4RL2-rs61745214 (P-value 7.71 × 10−12), and PGRMC1-rs145582672 (P-value 8.56 × 10−12), exonic variants on chromosomes 15, 22, and 16 were highly associated with HL cases. The highly significant haplotypes at chromosome 3: rs143894786G; rs149982219G with P-value = 3.43 × 10−14 was found to be the risk haplotype for the HL patients. The opposite alleles at chromosome 3: rs143894786A; rs149982219G is protective with P-value = 2.46 × 10−12. Maximum number of SNPs at the chromosome 19: rs144433879C; rs181265966G; rs201144421C; rs145591797G; rs200560875G; rs77270337G (risk P-value = 2.24 × 10−12) and its opposite allele rs144433879A; rs181265966A; rs201144421T; rs145591797A; rs200560875A; rs77270337A (protective P-value = 2.60 × 10−9) were found to be associated haplotype with the HL and controls, respectively, in Saudi population. Conclusion: Our study concludes that the HL is genetically heterogeneous with multigene causation.