Functional multigenic variations associated with hodgkin lymphoma

Int J Lab Hematol. 2021 Dec;43(6):1472-1482. doi: 10.1111/ijlh.13644. Epub 2021 Jul 3.

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.

Keywords: hodgkin lymphoma; microarray; multigenic variations.

MeSH terms

  • Alleles
  • Case-Control Studies
  • Exome Sequencing
  • Genetic Association Studies* / methods
  • Genetic Heterogeneity*
  • Genetic Predisposition to Disease*
  • Genetic Variation*
  • Genotype
  • Haplotypes
  • Hodgkin Disease / diagnosis*
  • Hodgkin Disease / etiology*
  • Humans
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Saudi Arabia