No abstract

The sodium taurocholate cotransporting polypeptide (NTCP) encoded by SLC10A1 was recently demonstrated to be a functional receptor for hepatitis B virus (HBV). The role of SLC10A1 polymorphisms, particularly the Ser267Phe variant (rs2296651) in exon 4, has been frequently investigated in regard to risk of persistent HBV infection. However, these investigations have generated conflicting results. To examine whether common genetic variation at the SLC10A1 locus is associated with risk of persistent HBV infection, haplotype-tagging and imputed single nucleotide polymorphisms (SNPs) were assessed in two case-control sample sets, totally including 2,550 cases (persistently HBV infected subjects, PIs) and 2,124 controls (spontaneously recovered subjects, SRs) of Southern Chinese ancestry. To test whether rare or subpolymorphic SLC10A1 variants are associated with disease risk, the gene’s exons in 244 cases were sequenced. Overall, we found neither SNPs nor haplotypes of SLC10A1 showed significant association in the two sample sets. Furthermore, no significant associations of rare variants or copy number variation covering SLC10A1 were observed. Finally, expression quantitative trait locus analyses revealed that SNPs potentially affecting SLC10A1 expression also showed no significant associations. We conclude that genetic variation at the SLC10A1 locus is not likely a major risk factor of persistent HBV infection among Southern Chinese.

Study Objectives: To clarify the effects of sleep duration on stroke and stroke subtypes, we adopted a Mendelian randomization (MR) approach to evaluate their causal relationship. Methods: A genome-wide association study including 446,118 participants from UK biobank was used to identify instruments for short sleep, long sleep and sleep duration. Summary-level data for all stroke, ischemic stroke, intracerebral hemorrhage, and their subtypes were obtained from meta-analyses conducted by the MEGASTROKE consortium. MR analyses were performed using the inverse-variance-weighted method, weighted median estimator, MR pleiotropy residual sum and outlier (MR-PRESSO) test, and MR-Egger regression. Sensitivity analyses were further performed using leave-one-out analysis, MR-PRESSO global test and Cochran's Q test to verify the robustness of our findings. Results: By two-sample MR, we didn't find causal associations between sleep duration and risk of stroke. However, in the subgroup analysis, we found weak evidence for short sleep in increasing risk of cardio-embolic stroke (odds ratio [OR], 1.33; 95% confidence interval [CI], 1.11-1.60; P = 0.02) and long sleep in increasing risk of large artery stroke [OR, 1.41; 95% CI, 1.02-1.95; P = 0.04]. But the associations were not significant after Bonferroni correction for multiple comparisons. Conclusions: Our study suggests that sleep duration is not causally associated with risk of stroke and its subtypes.

Taiwan has very high incidence and prevalence of chronic kidney disease (CKD), which easily progresses to end-stage renal disease (ESRD). The association between inflammation and CKD has been explored in several studies. ORAI1 functions as a pore-forming subunit of the store-operated calcium channels which are involved in the regulation of immune system. Hence, we conducted a case-control study to determine whether the genetic polymorphisms of ORAI1 gene is a susceptibility factor to CKD and its clinical features in a Taiwanese population. Five hundred seventy-nine CKD patients from a hospital-based CKD care program were included in the study. Five tagging single nucleotide polymorphisms (tSNPs) of ORAI1 were selected from the genotyping data of the Han Chinese population from the HapMap project. Among these polymorphisms, rs12313273 was found to be significantly associated with elevated serum calcium levels, which has been linked to increased risk of death in CKD patients. To have a better management of serum calcium, we suggest that ORAI1 polymorphisms might be used as a potential biomarker for initiating non-calcium-based phosphate binder in CKD patients in the future.