Variants in <scp><i>HSD11B1</i></scp> gene modulate susceptibility to diabetes kidney disease and to insulin resistance in type 1 diabetes
Rosana Cristina Tieko Mori, Daniele Pereira Santos‐Bezerra, Tatiana Souza Pelaes, Sharon Nina Admoni, Ricardo Vessoni Perez, Maria Beatriz Monteiro, Cleide Guimarães Machado, Márcia Silva Queiroz, Ubiratan Fabres Machado, Maria Lúcia Corrêa‐Giannella
Abstract
Abstract Background and aim 11β‐Hydroxysteroid dehydrogenase 1 has been implicated in insulin resistance (IR) in the setting of metabolic disorders, and single nucleotide polymorphisms (SNPs) in its encoding gene ( HSD11B1 ) have been associated with type 2 diabetes and metabolic syndrome. In type 1 diabetes (T1D), IR has been related to the development of chronic complications. We investigated the association of HSD11B1 SNPs with microvascular complications and with IR in a Brazilian cohort of T1D individuals. Materials and methods Five SNPs were genotyped in 466 T1D individuals (57% women; median of 37 years old, diabetes duration of 25 years and HbA1c of 8.4%). Results The minor allele T of rs11799643 was nominally associated with diabetic retinopathy (OR = 0.52; confidence interval [CI] 95% = 0.28‐0.96; P = .036). The minor allele C of rs17389016 was nominally associated with overt diabetic kidney disease (DKD) (OR = 1.90; CI 95% = 1.07‐3.37; P = .028). A follow‐up study revealed that 29% of the individuals lost ≥5 mL min −1 × 1.73 m 2 per year of the estimated glomerular filtration rate (eGFR). In these individuals (eGFR decliners), C allele of rs17389016 was more frequent than in non‐decliners (OR = 2.10; CI 95% = 1.14‐3.89; P = .018). Finally, minor allele T of rs846906 associated with higher prevalence of arterial hypertension, higher body mass index and waist circumference, thus conferring risk to a lower estimated glucose disposal rate, a surrogate marker of insulin sensitivity (OR = 1.23; CI 95% = 1.06‐1.42; P = .004). Conclusion SNPs in the HSD11B1 gene may confer susceptibility to DKD and to IR in T1D individuals.