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Weintraub et al. aimed to compare rs7041 G>T and rs4588 C>A genotype frequencies of GC-globulin in 48 Caucasian Americans and 95 African Americans with chronic hepatitis C virus (HCV) infection. In Caucasians the GC rs7041 G allele frequency was found to be very similar to that detected by our group (0.54 versus 0.55).1 However, the G allele was found to be far less frequent in African Americans (0.15).

Different allele distributions of GC rs7041 G>T have been reported in different populations by HAPMAP and 1000 genomes project databases. In particular, the G allele is rarely carried in central Africans (6%-9%) and African Americans (16%) and is maximally carried in Finnish (65%). The genotype frequencies of GC rs7041 G>T observed by Weintraub et al. in HCV chronically infected African Americans patients were: G/G 0.01, G/T 0.27, T/T 0.72; these values are very close to those obtained in similar unselected populations by combing HAPMAP and 1000 genomes project data: G/G 0.04, G/T 0.26, T/T 0.70.

Beside seasonal and environmental factors in conjunction with the less efficient UV radiation in dark skins, vitamin D serum levels are at least in part conditioned by genetic predictors. The ethnic variations of GC-globulin polymorphic loci allele frequencies2 seem to be related to a geographic decreasing gradient of UV skin exposure. It may be supposed that the lower values of vitamin D levels found in African Americans could be the result of a less sunny skin exposure when living at higher latitudes. This reflects the high prevalence of hypovitaminosis D observed in African Americans (45%) in comparison to Caucasian Americans (11%).

Recently, Weintraub et al. investigated, in 106 African Americans and 65 Caucasian Americans HCV genotype 1-infected patients, the relationship between 25-OH vitamin D basal serum levels and sustained viral response (SVR) attainment after antiviral treatment.3 Very interestingly, the authors found that in Caucasian Americans but not in African Americans higher vitamin D levels were associated with a more frequent occurrence of SVR.

The absence of a relationship between vitamin D levels and SVR in African Americans together with the infrequent carriage in these patients of GC-globulin WT+ genotypes1 suggest that the genetic background may play a pivotal role in favoring the beneficial immunological effect of vitamin D. Nevertheless, to answer if in African Americans SVR is associated with GC-globulin genetic variability, a sufficiently powered direct study should be performed.