Background: CD36 deficiency has been classified in two types, i.e., type I and type II CD36 deficiency. Possible pathological involvement of CD36 deficiency has been suggested in humans, but is still confounding. Homozygous or compound heterozygous mutations (CD36(-/-)) were demonstrated in type I CD36 deficiency, while the genomic or molecular background of type II CD36 deficiency is still unclear, which may bring confounding interpretations of the cause-and-effect events in human CD36 deficiency. In this study, we analyzed the genotype and frequency of type II CD36 deficiency in Japanese populations, and its hereditary pattern in three families.
Methods: Genotypes and protein expression levels of CD36 were examined in 238 Japanese subjects. Genotype was analyzed in the coding region of the CD36 gene. The expression level of CD36 protein was analyzed by flow cytometry after staining with monoclonal anti-CD36 antibody and assessed as mean fluorescence intensity (MFI).
Results: Among 238 subjects, subjects for wild-type gene (WT), a single mutation (CD36(+/-)), and CD36(-/-) were 141, 44 and 53, respectively. Monocyte MFI (mean+/-SD) in subjects for WT, CD36(+/-), and CD36(-/-) were 35.7+/-8.5, 15.2+/-3.4, and 0.4+/-0.3, respectively (P<0.0001, between groups). Those of platelets in subjects for WT, CD36(+/-), and CD36(-/-) were 27.1+/-10.6, 11.5+/-6.3, and 0.5+/-0.3, respectively (P<0.0001, between groups). Subjects of both WT and CD36(+/-) were observed in type II CD36 deficiency. Monocyte and platelet MFI in family members of type II CD36 deficiency and 218 unrelated Japanese suggested that the expression level of CD36 protein in monocytes was directly dependent on genotypes. On the other hand, those in platelets were affected by additional heritable factor(s) in addition to the coding region genotype.
Conclusions: MFI in monocytes showed a strong gene-dosage-dependency. On the other hand, MFI in platelets was affected by heritable factor(s) in addition to the coding region genotype, which resulted in heterogeneity of type II CD36 deficiency.