Significance of 3'UTR and Pathogenic Haplotype in Glucose-6-Phosphate Deficiency

Lab Med. 2017 Feb;48(1):73-88. doi: 10.1093/labmed/lmw065.

Abstract

Objective: To determine the polymorphisms in the 3' untranslated region (3'UTR) of the G6PD gene and analyze the specific SNPs or haplotypes that may affect messenger RNA (mRNA) secondary structure by in silico analysis.

Methods: We studied the 3'UTR polymorphisms in 107 healthy subjects living in Thailand (ethnicities unknown). The haplotype was analyzed using Haploview software. mRNA secondary structure and microRNA binding of the G6PD gene were predicted by use of the CLC Main Workbench 6.9 and RegRNA 2.0 programs.

Results: The results revealed 1 new variant in the 3'UTR of the G6PD gene (c.*99A > G). Haplotype ATCG showed significance by association-test results that yielded a high odds ratio (OR, 7.90; 95% confidence interval [CI], 3.15-19.81). Moreover, this haplotype affected G6PD mRNA secondary structure changes and microRNA binding via in silico analysis.

Conclusions: These results suggest that the haplotype ATCG is associated with reduction of G6PD enzyme expression, G6PD mRNA secondary structure changes, and microRNA binding via in silico analysis.

Keywords: 3′UTR; G6PD; haplotype; mRNA secondary structure; malaria.

MeSH terms

  • 3' Untranslated Regions / genetics*
  • Adult
  • Female
  • Glucosephosphate Dehydrogenase Deficiency / genetics*
  • Glucosephosphate Dehydrogenase* / chemistry
  • Glucosephosphate Dehydrogenase* / genetics
  • Glucosephosphate Dehydrogenase* / ultrastructure
  • Haplotypes / genetics*
  • Humans
  • Linkage Disequilibrium
  • Male
  • Middle Aged
  • Nucleic Acid Conformation
  • Polymorphism, Single Nucleotide / genetics*
  • RNA, Messenger / genetics
  • Young Adult

Substances

  • 3' Untranslated Regions
  • RNA, Messenger
  • Glucosephosphate Dehydrogenase