ObjectiveTo elucidate the association of immune response to hepatitis B vaccination with HLA-DRB1 * 12 allele as well as the level of IL-4 and IFN-γ.MethodsSeventy-four healthy college students from Guangxi province who had non- or hypor -response to recombinant hepatitis B vaccination and 64 medium- or hyper-responders with the conditions of similar were selected randomly and involved in this study.HLA-DRB1 * 12 was detected by PCR-SSP,the level of IFN-γ and IL-4 cytokines were examined by ELISA.Results(1)The allelic frequencies of HLA-DRB1 * 12 was lower in the non- or hypor-responders than that in the medium- or hyper-responders ( 10.8％ vs 32.8％,P=0.002) ; (2)The expression level of IFN-γ in the non- or hypor-responders ( 7.21±7.92 ) ng/ml was much less than that of the medium- or hyper- responders ( 16.36± 11.00) ng/ml ( P=0.000).(3) The expression level of IL-4 in the non- or hyporresponders (3.18±4.45) ng/ml was much less than that of the medium- or hyper- responders (7.76±5.71 ) ng/ml(P=0.000).(4)No significant differences was seen between the expression level of IFN-γ in the HLA-DRB1 * 12 positive ( 13.18± 11.24) ng/ml and the negative ( 11.00± 10.29 ) ng/ml ( P =0.349 ).(5)No significant differences was seen between the expression level of IL-4 in the HLA-DRB1 * 12 positive (5.947±4.530) ng/ml and the negative (5.132±5.800) ng/ml (P=0.423).ConclusionHLA-DRB1 * 12 might be the allele enhanced immune response to hepatitis B vaccination.The expression levels of IFN-γand IL-4 correlating to Thl/Th2 cells might affect on the immune response to hepatitis B vaccination.

The isolated type of orofacial cleft, termed non-syndromic cleft lip with or without cleft palate (NSCL/P), is the second most common birth defect in China, with Asians having the highest incidence in the world. NSCL/P involves multiple genes and complex interactions between genetic and environmental factors, imposing difficulty for the genetic assessment of the unborn fetus carrying multiple NSCL/P-susceptible variants. Although genome-wide association studies (GWAS) have uncovered dozens of single nucleotide polymorphism (SNP) loci in different ethnic populations, the genetic diagnostic effectiveness of these SNPs requires further experimental validation in Chinese populations before a diagnostic panel or a predictive model covering multiple SNPs can be built. In this study, we collected blood samples from control and NSCL/P infants in Han and Uyghur Chinese populations to validate the diagnostic effectiveness of 43 candidate SNPs previously detected using GWAS. We then built predictive models with the validated SNPs using different machine learning algorithms and evaluated their prediction performance. Our results showed that logistic regression had the best performance for risk assessment according to the area under curve. Notably, defective variants in MTHFR and RBP4, two genes involved in folic acid and vitamin A biosynthesis, were found to have high contributions to NSCL/P incidence based on feature importance evaluation with logistic regression. This is consistent with the notion that folic acid and vitamin A are both essential nutritional supplements for pregnant women to reduce the risk of conceiving an NSCL/P baby. Moreover, we observed a lower predictive power in Uyghur than in Han cases, likely due to differences in genetic background between these two ethnic populations. Thus, our study highlights the urgency to generate the HapMap for Uyghur population and perform resequencing-based screening of Uyghur-specific NSCL/P markers.
Asian Continental Ancestry Group ; genetics ; China ; ethnology ; Cleft Lip ; genetics ; Cleft Palate ; genetics ; Genome-Wide Association Study ; Humans ; Infant ; Logistic Models ; Machine Learning ; Methylenetetrahydrofolate Reductase (NADPH2) ; genetics ; Polymorphism, Single Nucleotide ; Retinol-Binding Proteins, Plasma ; genetics ; Risk Assessment