Search

Background Differences in the concentrations of circulating 25-hydroxyvitamin D [25(OH)D] are associated with a wide range of health outcomes; however, most studies on genetic variants that impact 25(OH)D levels have been conducted in European populations. Here we aimed to identify common genetic variants that affect vitamin D concentrations in individuals of self-reported Arab ethnicity. Methods The study included 1151 Arab subjects living in Kuwait. Common variants of single-nucleotide polymorphisms and genes previously associated with vitamin D levels, such as GC, PDE3B, CYP2R1, and NADSYN1, were genotyped. Raw vitamin D level data were corrected for age, body mass index, and sex and then normalized. Regression tree analyses were performed to identify the impact of genetic variants on vitamin D levels. Results Compared with other gene variants, the GC gene variants exhibited the greatest impact on vitamin D levels in our study population, of which rs2298850 had the lowest p value (0.003). Individuals homozygous for the derived allele C had lower vitamin D levels. Analyses of the interaction between the number of years for which the subjects had lived in Kuwait and genetic variation in the GC gene showed that those with the CC genotype of rs2298850 who had lived in Kuwait for 51 years had higher vitamin D levels (mean 28 ng/ml) regardless of the genotype of their GC gene. Conclusions The GC gene may play a major role in determining vitamin D levels in Arab populations. Electronic supplementary material The online version of this article (10.1186/s12967-018-1396-8) contains supplementary material, which is available to authorized users.

Introduction: Lamivudine is a potent inhibitor of hepatitis B virus (HBV) replication via suppression of the RNAdependent DNA polymerase. However, patients with prolonged therapy were previously detected harboring drugresistant mutants. Such mutants though partially replication defective, confer resistance to lamivudine and can elicit exacerbation of hepatonecro-inflammation. Cases presentation: In this case series, we examined mutations in the YMDD motif gene in five lamivudinetreated patients (60 yr male, 50 yr female, 46 yr male, 36 yr male and 42 yr male) and in four untreated patients (34 yr female, 29 yr male, 29 female and 37 yr male). Rare mutational patterns of rtM204L in conjunction with rtL108M were recognized conferring resistance to lamivudine. The rtL180M compensatory mutation was identified in conjunction with rtM204V/I/L; among which three patients had viral and biochemical breakthrough associated with serum HBV DNA levels exceeding 106 copies/mL. Conclusions: These results indicate that; (i) lamivudine resistant HBV strains are naturally occurring mutants as detected in lamivudine untreated patients and; (ii) New mutational patterns (rtM204L: YLDD and rtL180M) were identified conferring resistance to lamivudine and resulted in biochemical and virological breakthrough. Based on these findings, we propose that such mutations can be used as a marker to predict development of viral breakthrough in the HBV patients whether or not treated with lamivudine.