Distinct and shared genetic architectures of gestational diabetes mellitus and type 2 diabetes.

Gestational diabetes mellitus (GDM) is a common metabolic disorder affecting more than 16 million pregnancies annually worldwide1,2. GDM is related to an increased lifetime risk of type 2 diabetes (T2D)1-3, with over a third of women developing T2D within 15 years of their GDM diagnosis. The diseases are hypothesized to share a genetic predisposition1-7, but few studies have sought to uncover the genetic underpinnings of GDM. Most studies have evaluated the impact of T2D loci only8-10, and the three prior genome-wide association studies of GDM11-13 have identified only five loci, limiting the power to assess to what extent variants or biological pathways are specific to GDM. We conducted the largest genome-wide association study of GDM to date in 12,332 cases and 131,109 parous female controls in the FinnGen study and identified 13 GDM-associated loci, including nine new loci. Genetic features distinct from T2D were identified both at the locus and genomic scale. Our results suggest that the genetics of GDM risk falls into the following two distinct categories: one part conventional T2D polygenic risk and one part predominantly influencing mechanisms disrupted in pregnancy. Loci with GDM-predominant effects map to genes related to islet cells, central glucose homeostasis, steroidogenesis and placental expression.

Sequence analysis of the genes encoding for H+/K+-ATPase in autoimmune gastritis.

BACKGROUND: H+/K+-ATPase is the target autoantigen in autoimmune gastritis (AIG), an organ-specific autoimmune disease with a strong hereditary component. AIM: To detect possible polymorphisms in H+/K+-ATPase alpha- and beta-subunits in AIG patients. METHODS: Blood samples from 12 Finnish AIG patients were sequenced for the coding regions of genes encoding for H+/K+-ATPase alpha- and beta-subunits; 50-52 Finnish anonymous blood donors served as controls. Additionally, parietal cell and Helicobacter pylori antibodies and serum pepsinogen I levels (PG I) were analysed. RESULTS: In the alpha-subunit, all patients and controls had C-allele at the non-synonymous c.824T>C single nucleotide polymorphism (SNP) resulting in valine substitution for alanine (Val265Ala). In the beta-subunit, a previously unknown non-synonymous SNP resulting in a substitution of alanine residue for valine (Ala248Val) was found in exon 7 in a single patient and none of the controls. All patients had low serum PG I levels and elevated parietal cell antibodies; three had positive H. pylori serology. CONCLUSIONS: At the non-synonymous SNP c.824T>C in the alpha-subunit of H+/K+-ATPase most Finnish individuals with or without AIG have C allele. Genetic variants of the coding regions of genes for H+/K+-ATPase alpha- and beta-subunits are not associated with AIG in Finnish patients.