Comprehensive Genotyping in Two Homogeneous Graves' Disease Samples Reveals Major and Novel HLA Association Alleles

BACKGROUND: Graves' disease (GD) is the leading cause of hyperthyroidism and thyroid eye disease inherited as a complex trait. Although geoepidemiology studies showed relatively higher prevalence of GD in Asians than in Caucasians, previous genetic studies were contradictory concerning whether and/or which human leukocyte antigen (HLA) alleles are associated with GD in Asians. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a case-control association study (499 unrelated GD cases and 504 controls) and a replication in an independent family sample (419 GD individuals and their 282 relatives in 165 families). To minimize genetic and phenotypic heterogeneity, we included only ethnic Chinese Han population in Taiwan and excluded subjects with hypothyroidism. We performed direct and comprehensive genotyping of six classical HLA loci (HLA-A, -B, -C, -DPB1, -DQB1 and -DRB1) to 4-digit resolution. Combining the data of two sample populations, we found that B*46:01 (odds ratio under dominant model [OR]  = 1.33, Bonferroni corrected combined P [P(Bc)]  = 1.17 x 10⁻²), DPB1*05:01 (OR  = 2.34, P(Bc) = 2.58 x 10⁻¹⁰), DQB1*03:02 (OR  = 0.62, P(Bc)  = 1.97 x 10⁻²), DRB1*15:01 (OR  = 1.68, P(Bc) = 1.22 x 10⁻²) and DRB1*16:02 (OR  = 2.63, P(Bc)  = 1.46 x 10⁻⁵) were associated with GD. HLA-DPB1*05:01 is the major gene of GD in our population and singly accounts for 48.4% of population-attributable risk. CONCLUSIONS/SIGNIFICANCE: These GD-associated alleles we identified in ethnic Chinese Hans, and those identified in other Asian studies, are totally distinct from the known associated alleles in Caucasians. Identification of population-specific association alleles is the critical first step for individualized medicine. Furthermore, comparison between different susceptibility/protective alleles across populations could facilitate generation of novel hypothesis about GD pathophysiology and indicate a new direction for future investigation

Erythropoietin improves long-term neurological outcome in acute ischemic stroke patients: a randomized, prospective, placebo-controlled clinical trial.

Mortality and disability following ischemic stroke (IS) remains unacceptably high with respect to the conventional therapies. This study tested the effect of erythropoietin (EPO) on long-term neurological outcome in patients after acute IS. This study aimed to evaluate the safety and efficacy of two consecutive doses of EPO (5,000 IU/dose, subcutaneously administered at 48 hours and 72 hours after acute IS) on improving the 90-day combined endpoint of recurrent stroke or death that has been previously reported. A secondary objective was to evaluate the long-term (that is, five years) outcome of patients who received EPO.This article is freely available via Open Access. Click on the 'Additional Link' above to access the full-text via the publisher's site.Published (Open Access

EXTENDING WORK-LIFE : WORK PROPENSITY AND ORIENTATIONS OF MIDDLE-AGED AND OLDER SINGAPOREANS

Master'sMASTER OF SOCIAL SCIENCES (APPLIED SOCIOLOGY

OFFBEAT ENTREPRENEURS : SOCIOLOGICAL ASPECTS OF TOUTING IN SINGAPORE

Bachelor'sBACHELOR OF SOCIAL SCIENCES (HONOURS

NEED FOR BUSINESS PARKS IN SINGAPORE, THE

Bachelor'sBACHELOR OF SCIENC

THE NEED FOR BUSINESS PARKS IN SINGAPORE

Bachelor'sBACHELOR OF SCIENCE (ESTATE MANAGEMENT

Corporate governance : external auditors and their opinions.

The increasing awareness and emphasis on corporate governance may be traced to the occurrence of many company failures over the past few years. The term corporate governance can be defined as the way corporate entities are governed, and the issues facing the board of directors, such as the interaction with top management, and relationships with the owners and others interested in the affairs of the company, including creditors, debt financiers, analysts, auditors and corporate regulators. Our study was conducted to identify the opinions of external auditors on various issues of corporate governance

Impact of foreign stock markets on our local market

92 p.With the rapid globalisation and integration of international capital markets, this study is undertaken to explore the degree of interdependencies between Singapore and the three major developed markets - the New York, Tokyo and Hong Kong stock markets.ACCOUNTANC

Energy transfer through heterogeneous dyes-substituted fluorene-containing alternating copolymers and their dual-emission properties in the films

We report synthesis of the modified fluorene polymers tethered to the heterogeneous types of the fluorescent dyes at the cardo carbon for obtaining the dual-emissive solid materials. A series of the alternating fluorene copolymers modified with pyrene or 9, 10-diphenylanthracene and BODIPY at the cardo carbon based on the red-emissive donor–acceptor structure were prepared, and their characteristics were examined. From the measurements of the optical properties, the energy transfer efficiencies were evaluated. In summary, variable energy transfer efficiencies were observed between the side chains and from the side chain to the main chain. It was indicated that the energy transfer efficiencies were strongly depended on the types of the energy donor and the detection conditions as such in the solution or film. Furthermore, it was found that the cardo fluorene units can contribute to the suppression of the energy transfer in the condensed state. Finally, the dual-emissive polymers were obtained in the film states. This is the first example, to the best of our knowledge, not only to offer systematic information on the energy transfer between the dye molecules and the polymer main-chains via the cardo structure but also to demonstrate the polymer-based optical materials with the dual-emission properties