Mutations and intronic variants in the HNF-1beta gene in a group of German and Czech Caucasians with type 2 diabetes mellitus and progressive diabetic nephropathy

Abstract

Mutations in the hepatocyte nuclear factor - 1 beta (HNF-1 beta) gene cause maturity onset diabetes of the young type 5 (MODY 5). A clinical feature of the resulting phenotype besides impaired glucose tolerance is a variety of renal abnormalities, ranging from renal cysts to end-stage renal failure. Using a candidate gene approach we investigated the prevalence of mutations in the HNF-1 beta gene in a group of 63 patients from two different European populations (33 Germans, 30 Czechs) with type 2 diabetes mellitus and diabetic nephropathy diagnosed by increased albuminuria (39 patients) or end-stage renal failure (24 patients). No mutations were found in any of the 9 exons or in a minimal promoter region. Three intronic variants (single nucleotide polymorphisms - SNPs) were detected. The frequencies of these variants showed no difference between the two studied populations and were comparable to data reported from healthy subjects. No association between SNPs or formed haplotypes and any clinical parameters (like age of disease onset, BMI and severity of renal failure) was found. The results confirm that the genetic variations in the HNF-1 beta gene would be a very uncommon cause of progressive nephropathy in patients with type 2 diabetes mellitus.

Assessment of 115 Candidate Genes for Diabetic Nephropathy by Transmission/Disequilibrium Test

“…However, no HNF1B1 mutations were found among 63 German and Czech type 2 diabetic patients with diabetic nephropathy (32). In our type 1 diabetic families with diabetic nephropathy, we found nominally significant evidence with an SNP located in the 3Ј-UTR (rs2688, P ϭ 0.029), but three SNPs in introns of HNF1B1 and one located 2.2 kb 3Ј of the gene failed to support this finding.…”

Genetik des Diabetes mellitus – Prädiktive genetische Tests werden kontrovers diskutiert

“…Mit der Entdeckung des CAPN10-Gens, unter Mitarbeit unserer Dresdener Arbeitsgruppe, konnte ein entscheidender vererbter Risikofaktor für den T2DM beschrieben werden (4). Im Anschluss daran konnte unsere Arbeitsgruppe verschiedene neue genetische Faktoren für T2DM untersuchen und deren klinische Relevanz beschreiben (2, [7][8][9][10][11][12]. Man geht heute davon aus, dass sich beim T2DM, einer multi faktoriellen polygenetischen Erkrankung, verschiedene genetische Faktoren in einem oder mehreren Genen summieren und im Zusammenspiel mit den entsprechenden Umweltfaktoren in einem schleichenden Prozess zur Manifestation der Erkrankung führen.…”