Identification of New Genetic Risk Variants for Type 2 Diabetes

Although more than 20 genetic susceptibility loci have been reported for type 2 diabetes (T2D), most reported variants have small to moderate effects and account for only a small proportion of the heritability of T2D, suggesting that the majority of inter-person genetic variation in this disease remains to be determined. We conducted a multistage, genome-wide association study (GWAS) within the Asian Consortium of Diabetes to search for T2D susceptibility markers. From 590,887 SNPs genotyped in 1,019 T2D cases and 1,710 controls selected from Chinese women in Shanghai, we selected the top 2,100 SNPs that were not in linkage disequilibrium (r2<0.2) with known T2D loci for in silico replication in three T2D GWAS conducted among European Americans, Koreans, and Singapore Chinese. The 5 most promising SNPs were genotyped in an independent set of 1,645 cases and 1,649 controls from Shanghai, and 4 of them were further genotyped in 1,487 cases and 3,316 controls from 2 additional Chinese studies. Consistent associations across all studies were found for rs1359790 (13q31.1), rs10906115 (10p13), and rs1436955 (15q22.2) with P-values (per allele OR, 95%CI) of 6.49×10−9 (1.15, 1.10–1.20), 1.45×10−8 (1.13, 1.08–1.18), and 7.14×10−7 (1.13, 1.08–1.19), respectively, in combined analyses of 9,794 cases and 14,615 controls. Our study provides strong evidence for a novel T2D susceptibility locus at 13q31.1 and the presence of new independent risk variants near regions (10p13 and 15q22.2) reported by previous GWAS

Generation and specification of unique neuronal sub-types: lessons from Drosophila neuropeptide neurons

The central nervous system (CNS) contains a daunting diversity of neuronal cell types. One of the major challenges of developmental neurobiology is to understand the regulatory mechanisms underlying this vast complexity. Studies in the Drosophila melanogaster (Drosophila) model system has contributed greatly to our understanding of neuronal cell sub-type specification, and the majority of mechanisms and genes identified in this system has proved to be of great value, and often more or less directly transferable to studies of mammalian neuro-development. In Drosophila, studies of the developmental generation of numerous different neuropeptide neurons have been highly informative, since these neurons are generated in a highly restricted and reproducible manner. In addition, neuropeptides are expressed at high levels and their regulatory regions have proven comparatively condensed, facilitating the generation of a multitude of antibodies and transgenic markers. Here, we first provide a general background to Drosophila CNS development. Then, we focus in more detail on various well studied neuropeptide neurons identified in this system, and describe what has been learned regarding the generation and differentiation of these highly unique neuronal sub-types. We intend this review to provide an overview of the variety of mechanisms that operate throughout the developmental period to generate highly unique neuronal sub-types. Finally, we conclude with some general remarks and perspectives regarding neuronal sub-type specification in general

Testosterone Therapy in Male Infertility

Normal spermatogenesis is dependent upon production of endogenous testosterone and elevated concentrations of intratesticular testosterone. Testosterone levels typically begin to decrease over time in men starting in their late 30s; however, as many as 12.4% of men below the age of 39 suffer the effects of low testosterone and seek treatment. This statistic suggests that a significant number of men seeking treatment for low testosterone are within their reproductive years, underscoring the importance of appropriate counseling for patients seeking testosterone therapy as it pertains to family planning. The standard treatment for men with low testosterone and symptoms of hypogonadism is administration of exogenous testosterone. The challenge for testosterone replacement among men who desire fertility is that exogenous testosterone is a known contraceptive. The key for treatment of low testosterone while preserving fertility is maintenance of high concentrations of intratesticular testosterone and promotion of endogenous testosterone production. Therapies that accomplish this goal include administration of gonadotropins like GnRH and hCG, selective estrogen receptor modulators like clomiphene citrate, and aromatase inhibitors like anastrozole. Experimental therapies include intranasal testosterone gels and Leydig stem cell transplantation