Associations of Type 2 Diabetes with Common Variants in PPARD and the Modifying Effect of Vitamin D among Middle-Aged and Elderly Chinese

BACKGROUND: Previous studies have identified that variants in peroxisome proliferator-activated receptor PPAR-δ (PPARD), a target gene of vitamin D, were significantly associated with fasting glucose and insulin sensitivity in European populations. This current study sought to determine (1) whether the genetic associations of PPARD variants with type 2 diabetes and its related traits could be replicated in Chinese Han population, and (2) whether the associations would be modified by the effect of vitamin D status. METHODS AND FINDINGS: We genotyped 9 tag single nucleotide polymorphisms (SNPs) that cover the gene of PPARD (rs2267664, rs6902123, rs3798343, rs2267665, rs2267668, rs2016520, rs2299869, rs1053049, and rs9658056) and tested their associations with type 2 diabetes risk and its related traits, including fasting glucose, insulin and HbA1c in 3,210 Chinese Hans. Among the 9 PPARD tag SNPs, rs6902123 was significantly associated with risk of type 2 diabetes (odds ratio 1.75 [95%CI 1.22-2.53]; P = 0.0025) and combined type 2 diabetes and impaired fasting glucose (IFG) (odds ratio 1.47 [95%CI 1.12-1.92]; P = 0.0054). The minor C allele of rs6902123 was associated with increased levels of fasting glucose (P = 0.0316) and HbA1c (P = 0.0180). In addition, we observed that vitamin D modified the effect of rs6902123 on HbA1c (P for interaction = 0.0347). CONCLUSIONS/SIGNIFICANCE: Our findings demonstrate that common variants in PPARD contribute to the risk of type 2 diabetes in Chinese Hans, and provided suggestive evidence of interaction between 25(OH)D levels and PPARD-rs6902123 on HbA1c

Cushing's Syndrome and Fetal Features Resurgence in Adrenal Cortex–Specific Prkar1a Knockout Mice

Carney complex (CNC) is an inherited neoplasia syndrome with endocrine overactivity. Its most frequent endocrine manifestation is primary pigmented nodular adrenocortical disease (PPNAD), a bilateral adrenocortical hyperplasia causing pituitary-independent Cushing's syndrome. Inactivating mutations in PRKAR1A, a gene encoding the type 1 α-regulatory subunit (R1α) of the cAMP–dependent protein kinase (PKA) have been found in 80% of CNC patients with Cushing's syndrome. To demonstrate the implication of R1α loss in the initiation and development of PPNAD, we generated mice lacking Prkar1a specifically in the adrenal cortex (AdKO). AdKO mice develop pituitary-independent Cushing's syndrome with increased PKA activity. This leads to autonomous steroidogenic genes expression and deregulated adreno-cortical cells differentiation, increased proliferation and resistance to apoptosis. Unexpectedly, R1α loss results in improper maintenance and centrifugal expansion of cortisol-producing fetal adrenocortical cells with concomitant regression of adult cortex. Our data provide the first in vivo evidence that loss of R1α is sufficient to induce autonomous adrenal hyper-activity and bilateral hyperplasia, both observed in human PPNAD. Furthermore, this model demonstrates that deregulated PKA activity favors the emergence of a new cell population potentially arising from the fetal adrenal, giving new insight into the mechanisms leading to PPNAD

Color-Octet

We study contributions from color-octet quarkonium formation mechanisms to J=/ hadroproduction at low p ? . We include transitions of color-octet c¯c states into "direct" J=/ and into Ø 1;2 which decay radiatively into a J=/. Together with earlier work, this calculation constitutes a complete analysis of p ? -integrated J=/ production at leading twist. We find that the leading-twist contribution is not sufficient to reproduce the observed production rates and polarization of the J=/ and Ø 1;2 . Hence there must exist other important quarkonium production mechanisms at low p ? . Typeset using REVT E X I. INTRODUCTION The production and decays of heavy quarkonia have been widely studied using perturbative QCD [1]. Due to the large masses of the c and b quarks, the production or annihilation of heavy-quark--antiquark pairs takes place at a much shorter timescale than the formation of the bound state. This makes it possible to factorize the transition amplitudes. In hadroproduction re..

Cern--Th/97--261; Nordita-97/60 P; Tum/t39-97-25

Inclusive production of Ø cJ in e + e \Gamma annihilation is an excellent probe of the role of higher Fock states in the production of heavy quarkonia. Within the non-relativistic QCD approach, contributions from the short-distance production of colour-octet c¯c pairs are significantly larger than those from coloursinglet production. At the same time, Ø cJ production rates are significantly smaller than expected in the colour evaporation approach. Measurements of Ø cJ production at CLEO and future B-factories will thus constitute a major test of theoretical approaches to the production of heavy quarkonia. PACS numbers: 13.65.+i, 12.38.Bx, 13.85.Ni Typeset using REVT E X Calculations of heavy-quark production in e + e \Gamma collisions are now approaching a level of high accuracy. Fifteen years after the calculation of the next-to-leading-order (NLO) perturbative QCD corrections to the total open heavy-quark cross section [1], we have now seen the completion of the NLO correc..

Rupture of Abdominal Aortic Aneurysms in Patients Under Screening Age and Elective Repair Threshold

Peer reviewe

Evolution Effects in ... Fragmentation into Charmonium

In Z 0 decay into prompt charmonium, i.e. charmonium not originating from B-meson decays, the most important contribution is expected to come from colour-octet mechanisms. However, previous fixed-order calculations of the colour-octet contribution contain large logarithms which, in a more complete treatment, should be resummed to all orders. We study this resummation by using a Monte Carlo QCD cascade model and find that the fixed-order colour-octet result is diminished by 15%. We compare the Monte Carlo calculations with results obtained by using analytical evolution equations. 1 Introduction The production of charmonium and bottomonium states in various processes, especially at high-energy colliders [1], has recently received considerable experimental and theoretical interest. New data have become available from p¯p [2], ep [3] and e + e \Gamma [4--6] colliders. Theoretically, it has been realized that quarkonium production at colliders is dominated by parton fragmentation ..