Genetic factors affect the susceptibility to bacterial infections in diabetes

Abstract

Diabetes increases the risk of bacterial infections. We investigated whether common genetic variants associate with infection susceptibility in Finnish diabetic individuals. We performed genome-wide association studies and pathway analysis for bacterial infection frequency in Finnish adult diabetic individuals (FinnDiane Study; N = 5092, Diabetes Registry Vaasa; N = 4247) using national register data on antibiotic prescription purchases. Replication analyses were performed in a Swedish diabetic population (ANDIS; N = 9602) and in a Finnish non-diabetic population (FinnGen; N = 159,166). Genome-wide data indicated moderate but significant narrow-sense heritability for infection susceptibility (h2 = 16%, P = 0.02). Variants on chromosome 2 were associated with reduced infection susceptibility (rs62192851, P = 2.23 × 10–7). Homozygotic carriers of the rs62192851 effect allele (N = 44) had a 37% lower median annual antibiotic purchase rate, compared to homozygotic carriers of the reference allele (N = 4231): 0.38 [IQR 0.22–0.90] and 0.60 [0.30–1.20] respectively, P = 0.01). Variants rs6727834 and rs10188087, in linkage disequilibrium with rs62192851, replicated in the FinnGen-cohort (P < 0.05), but no variants replicated in the ANDIS-cohort. Pathway analysis suggested the IRAK1 mediated NF-κB activation through IKK complex recruitment-pathway to be a mediator of the phenotype. Common genetic variants on chromosome 2 may associate with reduced risk of bacterial infections in Finnish individuals with diabetes.

Diabetes ExacerbatesPseudomonas aeruginosaKeratitis in Streptozotocin-Induced and db/db Mice via Altering Programmed Cell Death Pathways

“…Studies have shown that impaired immunity in the hyperglycemic environment can lead to an increased incidence and severity of bacterial infections. 48 , 49 Chronic complications of diabetes, such as neuropathy, peripheral vascular disease, and increased expression of proinflammatory cytokines, have also been linked to microbial infection-related ulcerations in the skin and corneas. 50 In this study, we aimed to compare the impact of T1 and T2 DM on PCD pathways in response to Pa infection.…”

The RELT Family of Proteins: An Increasing Awareness of Their Importance for Cancer, the Immune System, and Development

“…A SNP located most proximally to RELL1 was one of two SNPs to be most associated with persistent and intermittent nasal carriage of S. aureus in one population [93]. Finally, diabetes increases the risk of bacterial infections, and GWAS analysis for missense mutations identified RELL1 as one of two genes most likely mutated in a population of diabetic patients that purchased antibiotics [94], implicating RELL1 as being associated with both diabetes and bacterial infections.…”