It is common to observe the clustering of chronic hepatitis B surface antigen (HBsAg) carriers in families. Intra-familial transmission of hepatitis B virus (HBV) could be the reason for the familial clustering of HBsAg carriers. Additionally, genetic and gender factors have been reported to be involved. We conducted a three-stage genome-wide association study to identify genetic factors associated with chronic HBV susceptibility. A total of 1,065 male controls and 1,623 male HBsAg carriers were included. The whole-genome genotyping was done on Illumina HumanHap550 beadchips in 304 healthy controls and HumanHap610 beadchips in 321 cases. We found that rs9277535 (HLA-DPB1, P = 4.87×10−14), rs9276370 (HLA-DQA2, P = 1.9×10−12), rs7756516 and rs7453920 (HLA-DQB2, P = 1.48×10−11 and P = 6.66×10−15 respectively) were significantly associated with persistent HBV infection. A novel SNP rs9366816 near HLA-DPA3 also showed significant association (P = 2.58×10−10). The “T-T-G-G-T” haplotype of the five SNPs further signified their association with the disease (P = 1.48×10−12; OR = 1.49). The “T-T” haplotype composed of rs7756516 and rs9276370 was more prevalent in severe disease subgroups and associated with non-sustained therapeutic response (P = 0.0262). The “G-C” haplotype was associated with sustained therapeutic response (P = 0.0132; OR = 2.49). We confirmed that HLA-DPB1, HLA-DQA2 and HLA-DQB2 loci were associated with persistent HBV infection in male Taiwan Han-Chinese. In addition, the HLA-DQA2 and -DQB2 complex was associated with clinical progression and therapeutic response.

IntroductionHyperglycemia and insulin resistance are commonplace in critical illness, especially in patients with sepsis. Recently, several hormones secreted by adipose tissue have been determined to be involved in overall insulin sensitivity in metabolic syndrome-related conditions, including adipocyte fatty-acid binding protein (A-FABP). However, little is known about their roles in critical illness. On the other hand, there is evidence that several adipose tissue gene expressions change in critically ill patients.MethodsA total of 120 patients (72 with sepsis, 48 without sepsis) were studied prospectively on admission to a medical ICU and compared with 45 healthy volunteers as controls. Various laboratory parameters and metabolic and inflammatory profiles were assessed within 48 hours after admission. Clinical data were collected from medical records.ResultsCompared with healthy controls, serum A-FABP concentrations were higher in all critically ill patients, and there was a trend of higher A-FABP in patients with sepsis. In multivariate correlation analysis in all critically ill patients, the serum A-FABP concentrations were independently related to serum creatinine, fasting plasma glucose, total cholesterol, TNF-alpha, albumin, and the Acute Physiology and Chronic Health Evaluation II scores. In survival analysis, higher A-FABP levels (> 40 ng/ml) were associated with an unfavorable overall survival outcome, especially in sepsis patients.ConclusionsCritically ill patients have higher serum A-FABP concentrations. Moreover, A-FABP may potentially serve as a prognostic biomarker in critically ill patients with sepsis.

Human height can be described as a classical and inherited trait model. Genome-wide association studies (GWAS) have revealed susceptible loci and provided insights into the polygenic nature of human height. Familial short stature (FSS) represents a suitable trait for investigating short stature genetics because disease associations with short stature have been ruled out in this case. In addition, FSS is caused only by genetically inherited factors. In this study, we explored the correlations of FSS risk with the genetic loci associated with human height in previous GWAS, alone and cumulatively. We systematically evaluated 34 known human height single nucleotide polymorphisms (SNPs) in relation to FSS in the additive model (p < 0.00005). A cumulative effect was observed: the odds ratios gradually increased with increasing genetic risk score quartiles (p < 0.001; Cochran-Armitage trend test). Six affected genes-ZBTB38, ZNF638, LCORL, CABLES1, CDK10, and TSEN15-are located in the nucleus and have been implicated in embryonic, organismal, and tissue development. In conclusion, our study suggests that 13 human height GWAS-identified SNPs are associated with FSS risk both alone and cumulatively.Human height can be described as a classical, inherited, and polygenic trait model. The ultimate phenotype represents the outcome of genetics and developmental biology, including the enlargement of bone length and the sizes of tissues and organ sizes. Undoubtedly, the developmental processes may be affected by environmental factors, including nutrition 1 , exercise 2 , diseases 3-5 , and infections 6, 7 . However, ~80% of the variance in height among individuals can also be explained by genetic variation [8][9][10] . Modern high-density genotyping platforms have now made it possible to identify candidate genes across the whole genome in relation to complex traits and diseases [11][12][13] .Genetic factors that contribute to the genetic architecture of human height are widely identified by means of genome-wide screening methods [14][15][16][17][18][19][20][21][22][23][24] . Human height-related susceptibility loci related to the protein tyrosine phosphatase family, insulin-like growth factor, and skeletal growth have been reported in Asian populations 18,19,21,22,25 . In addition, predisposing loci determining height have also been discovered in European populations in genes related to skeletal development, mitosis, fibroblast growth factors, the WNT/β-catenin pathway, chondroitin sulfate-related genes, mammalian target of rampamycin, osteoglycin, binding of hyaluronic acid, Hedgehog

AIMTo explore factors associated with persistent hepatitis B virus (HBV) infection in a cohort of hepatocellular carcinoma (HCC)-affected families and then investigate factors that correlate with individual viral load among hepatitis B surface antigen (HBsAg)-positive relatives.METHODSWe evaluated non-genetic factors associated with HBV replication in relatives of patients with HCC. Relatives of 355 HCC cases were interviewed using a structured questionnaire. Demographics, relationship to index case, HBsAg status of mothers and index cases were evaluated for association with the HBV persistent infection or viral load by generalized estimating equation analysis.RESULTSAmong 729 relatives enrolled, parent generation (P = 0.0076), index generation (P = 0.0044), mothers positive for HBsAg (P = 0.0007), and HBsAg-positive index cases (P = 5.98 × 10-8) were associated with persistent HBV infection. Factors associated with HBV viral load were evaluated among 303 HBsAg-positive relatives. Parent generation (P = 0.0359) and sex (P = 0.0007) were independent factors associated with HBV viral load. The intra-family HBV viral load was evaluated in families clustered with HBsAg-positive siblings. An intra-family trend of similar HBV viral load was found for 27 of 46 (58.7%) families. Male offspring of HBsAg-positive mothers (P = 0.024) and older siblings were associated with high viral load.CONCLUSIONSex and generation play important roles on HBV viral load. Maternal birth age and nutritional changes could be the reasons of viral load difference between generations.

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