Twins Study Of Heritability Of Response To HBV Vaccine And CD4~+/CD8~+T-Lymphocyte Subsets

Objective:To estimate the heritability of non/low-response to HBV vaccination andCD4~+and CD8~+T-Lymphocyte Subsets in1year-old healthy twins.Methods: Twins pairs born at5general hospitals in Urumqi city of Xinjiang UygurAutonomous Region were recruited at child care settings based on the inclusion andexclusion criteria after obtaining inform consent from twins’ parents. Demographicinformation, family history, parental life styles especially smoking status，and status ofalcohol consumption, maternal, gestational and birth information, as well as feeding andgrowth development information of infants were collected by interview and medicalrecords. The growth and development examination were performed by using nationalunified instruments and protocols. The participants had fasted for at least8h before4mlblood samples drawing. Venous whole blood samples (2ml) were obtained from allsubjects by using EDTA-K3tubes and CD4~+and CD8~+T cells counts were examined onthe same day by flow cytometry. Another blood samples were separated the serum within4h and transported to the central laboratory. Serum Anti-HBs concentration was examinedquantitatively by using the fluorescent Immunoassay kits (Abbott Laboratories, NorthChicago, IL). Zygosity of twins was determined by DNA-based microsatellite markers(ABI Laboratories, American). Stata11.0for Windows was used for conventionalstatistical analyses. Univariate structural equation models was used to estimate theheritability of anti-HBs concentration (ordinal variable, defined as non-response,low-response and normal response by cutoff points of10mIU/mL and100mIU/mL) andCD4~+and CD8~+T-lymphocyte subsets number by using Mx program.Results: Totally172healthy twin pairs consist of82monozygotic (47.67%%) and90dizygotic pairs. After model fitting, the AE model including additive genetic (A) andunique environmental (E) effect shows the best performance to the ordinal phenotypes foranti-HBs. Modest to high heritability estimates were obtained in univariate analysisdetermining additive genetic effect (i.e. heritability)91%for variation of anti-HBs. Inaddition, unshared environmental effect explained9%of the variations.After model fitting to CD4~+and CD8~+T-Lymphocyte counts, AE model shows the best performance to thecontinuous phenotypes for both CD4~+and CD8~+T-Lymphocyte counts, additive geneticeffect (i.e.heritability) explained62%(95%CI:38%~75%) and57%(95%CI:35%~70%) ofvariation of CD4~+and CD8~+T-Lymphocyte counts, respectively. Unshared environmentaleffect explained38(95%CI:20~53%) and43%(95%CI:26~62%) of the variations,respectively.Conclusion: The heritability of anti-HBs was0.91in1-year old infants, being higher thanreported in adults. The heritability of CD4~+and CD8~+T-Lymphocyte counts were0.62and0.57in1-year old infants respectively. Given the unmodifiable genetic determinants, moreeffort from society and individuals is expected to reduce the vaccine failure by improvingperinatal parental care and child care.