Dominance of high-producing interleukin 6 and low-producing interleukin 10 and interferon γ alleles in glucose-6-phosphate dehydrogenase-deficient trauma patients

Jeffrey S. Upperman, Gina Pillage, Muhammad Q. Siddiqi, Adriana Zeevi, Natasha Kelly, Henri R. Ford, Candace Kammerer, Zoltán Spolarics

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Glucose-6-phosphate dehydrogenase (G6PD) deficiency, a condition associated with malaria resistance, is a common genetic polymorphism. Decreased interleukin (IL)-10 production was demonstrated in vivo and in vitro in the African and Mediterranean forms of G6PD deficiencies. We hypothesized that low-producing IL-10 alleles are more abundant in the G6PD-deficient than nondeficient population. One hundred eleven men with African American ancestry were tested for G6PD deficiency (Type A-202/376) and for the cytokine gene promoter polymorphisms of IL-10 (-1082 G/A, -819 T/C, and -592 A/C), tumor necrosis factor (TNF)-α (-308 G/A), transforming growth factor (TGF)-β1 (C/T codon 10 and C/G codon 25), IL-6 (-174 G/C), and interferon (IFN)-γ (+874 A/T). There were no differences in the allele frequencies for TNF-α, IL-6, or TGF-β1 between the G6PD-deficient and nondeficient population. In contrast, the low-producing IL-10 alleles (-592A) and low-producing IFN-γ (+874A) allele frequencies were greater in G6PD-deficient than nondeficient samples (P = 0.035 and 0.009). Seventy-one percent of G6PD-deficient and 50% of nondeficient samples carried the high-producing IL-6(G) allele with low-producing IL-10(A) allele (P = 0.03). Furthermore, 95% of deficient and 81% of nondeficient samples carried the IL-6(G) allele together with low-producing IFN-γ(A) allele (P = 0.017). These investigations indicate a predominant presence of high-producing IL-6 alleles together with low-producing IL-10 and IFN-γ alleles in individuals with ancestry from malaria-endemic regions. The frequency of low-producing IL-10 genotypes is greater in the G6PD-deficient compared with nondeficient patients. The fact that these genetic differences are preserved in the current African American G6PD-deficient population indicates their potential role in pathophysiological processes in the absence of the selective pressure caused by tropical diseases.

Original languageEnglish (US)
Pages (from-to)197-201
Number of pages5
JournalShock
Volume23
Issue number3
DOIs
StatePublished - Mar 2005
Externally publishedYes

Keywords

  • Cytokine
  • G6PD
  • Inflammation
  • Malaria
  • Polymorphisms
  • Sepsis

ASJC Scopus subject areas

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

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