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.