Dominance of high-producing interleukin 6 and low-producing interleukin 10 and interferon gamma alleles in glucose-6-phosphate dehydrogenase-deficient trauma patients.
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)-alpha (-308 G/A), transforming growth factor (TGF)-beta1 (C/T codon 10 and C/G codon 25), IL-6 (-174 G/C), and interferon (IFN)-gamma (+874 A/T). There were no differences in the allele frequencies for TNF-alpha, IL-6, or TGF-beta1 between the G6PD-deficient and nondeficient population. In contrast, the low-producing IL-10 alleles (-592A) and low-producing IFN-gamma (+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-gamma(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-gamma 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.
Upperman
Jeffrey S
JS
Division of Pediatric Surgery, Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Pillage
Gina
G
Siddiqi
Muhammad Q
MQ
Zeevi
Adriana
A
Kelly
Natasha
N
Ford
Henri R
HR
Kammerer
Candace
C
Spolarics
Zoltán
Z
D001741:Black or African American / Q000235:genetics; D000483:Alleles; D005787:Gene Frequency; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000150:complications / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics*; D016753:Interleukin-10 / Q000235:genetics*; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D014947:Wounds and Injuries / Q000150:complications
D015850:Interleukin-6; D016753:Interleukin-10; D007371:Interferon-gamma