HBV vaccine efficacy and detection and genotyping of vaccineé asymptomatic breakthrough HBV infection in Egypt

AIM:To evaluate the impact of mass vaccination against the hepatitis B virus (HBV) in Egypt,and to search for vaccinee asymptomatic breakthrough HBV infection and its genotype.METHODS:Seven hundred serum samples from vaccinated children and adults (aged 2-47 years) were used for quantitative and qualitative detection of HBsAb by ELISA.Three hundred and sixty serum samples representing undetectable or low or high HBsAb were screened for markers of active HBV infection (HBsAg,HBcAb (IgG) and HBeAb by ELISA,plus HBsAg by AxSYM) and HBV-DNA genotyping by nested multiplex PCR and by DNA sequencing.RESULTS:It was found that 65% of children aged 2-4 years,and 20.5% aged 4-13 years,as well as 45% adults were good responders to HBV vaccination mounting protective level HBsAb.Poor responders were 28%,59.5% and 34%,and non-responders were 7%,20% and 21% respectively,in the three studied groups.Markers of asymptomatic HBV infections were HBsAg detected by ELISA in 2.5% vs 11.39% by AxSYM.Other markers were HBcAb (IgG) in 1.38%,HBeAb in 0.83%,and HBV-DNA in 7.8%.All had HBV genotype E infection.CONCLUSION:It is concluded that HBV vaccine is efficient in controlling HBV infection among children and adults.The vaccine breakthrough infection was by HBV genotype E.A booster dose of vaccine is recommended,probably four years after initial vaccination.

A genome-wide scan for pleiotropy between bone mineral density and nonbone phenotypes

Osteoporosis is the most common metabolic bone disorder globally and is characterized by skeletal fragility and microarchitectural deterioration.Genetic pleiotropy occurs when a single genetic element is associated with more than one phenotype.We aimed to identify pleiotropic loci associated with bone mineral density(BMD)and nonbone phenotypes in genome-wide association studies.In the discovery stage,the NHGRI-EBI Catalog was searched for genome-wide significant associations(P value<5 x 108),excluding bone-related phenotypes.SNiPA was used to identify proxies of the significantly associated single nucleotide polymorphisms(SNPs)(r2=1).We then assessed putative genetic associations of this set of SNPs with femoral neck(FN)and lumbar spine(LS)BMD data from the GEFOS Consortium.Pleiotropic variants were claimed at a false discovery rate<1.4x 103 for FN-BMD and<1.5 x 10-3 for LS-BMD.Replication of these genetic markers was performed among more than 400000 UK Biobank participants of European ancestry with available genetic and heel bone ultrasound data.In the discovery stage,72 BMD-related pleiotropic SNPs were identified,and 12 SNPs located in 11 loci on 8 chromosomes were replicated in the UK Biobank.These SNPs were associated,in addition to BMD,with 14 different phenotypes.Most pleiotropic associations were exhibited by rs479844(AP5B1,O V O L 1 genes),which was associated with dermatological and allergic diseases,and rs4072037(M U C 1 gene),which was associated with magnesium levels and gastroenterological cancer.In conclusion,12 BMD-related genome-wide significant SNPs showed pleiotropy with nonbone phenotypes.Pleiotropic associations can deepen the genetic understanding of bone-related diseases by identifying shared biological mechanisms with other diseases or traits.