A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes

Identification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined (T1D+T2D) GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 diabetic subjects (and 18,582 DKD cases). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, p=4.5×10-8) associated with 'microalbuminuria' in European T2D cases. However, no replication of this signal was observed in Asian subjects with T2D, or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously-reported DKD signals, except for those at UMOD and PRKAG2, both associated with 'EGFR'. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk-variant discovery for DKD.</p

Salts of Tryptophan with p-Toluenesulphonic Acid and Camphorsulphonic Acids

Co-crystallisation of dl-tryptophan with p-toluenesulphonic acid, R-camphor-10-sulphonic acid and S-camphor-10-sulphonic acid resulted in salts. For all the structures, the amino acid is in the cationic form with the proton transferred from the acidic co-former to the amino acid. R-camphor-10-sulphonic acid and S-camphor-10-sulphonic acid were unsuccessful at resolving dl-tryptophan. Dissolution of the respective camphorsulphonic acid and dl-tryptophan in methanol/water gave crystals which contained equimolar amounts of the d- and the l-tryptophan. The following salts were also obtained in aqueous acetonitrile; (2l-TRP+)(2S-CSA−)·(H2O) from a mixture of l-TRP/S-CSA and (d-TRP+)(S-CSA−) from a mixture of d-TRP/S-CSA. The crystal structures and the thermal stability of the salts have been determined. (dl-TRP+)(p-TSA−) solved in P21/c with a = 19.422(2) Å, b = 5.5456(7) Å, c = 16.488(2) Å and β = 102.357(2)°. (d-TRP+)(l-TRP+)(2R-CSA−) solved in P21 with a = 12.780(3) Å, b = 10.411(2) Å, c = 32.574(7) Å and β = 97.60(3)°. (d-TRP+)(l-TRP+)(2S-CSA−) solved in P21 with a = 12.783(3) Å, b = 10.410(2) Å, c = 32.564(7) Å and β = 97.44(3)°. (2l-TRP+)(2S-CSA−)·(H2O) solved in P21 with a = 13.1761(12) Å, b = 10.3092(10) Å, c = 16.6268(16) Å and β = 104.435(2)°. (d-TRP+)(S-CSA−) solved in P212121 with a = 6.4185(13) Å, b = 12.700(3) Å, c = 25.173(5) Å and α = β = γ = 90°