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). 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 frequencies 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. 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+ genotypes 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.
Edmondo Falleti, M.D.
Carlo Fabris, M.D.
Pierluigi Toniutto, M.D.
1Department of Medical Sciences Clinical and Experimental Medical Liver Transplantation Unit Internal Medicine University of Udine Udine, Italy