Variants in HSD11B1 gene modulate susceptibility to diabetes kidney disease and to insulin resistance in type 1 diabetes.

Diabetes/metabolism research and reviews 2021 Jan

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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. 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%). 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 m2 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). SNPs in the HSD11B1 gene may confer susceptibility to DKD and to IR in T1D individuals. © 2020 John Wiley & Sons Ltd.

Citation

Rosana Cristina Mori, Daniele Pereira Santos-Bezerra, Tatiana Souza Pelaes, Sharon Nina Admoni, Ricardo Vessoni Perez, Maria Beatriz Monteiro, Cleide Guimarães Machado, Marcia Silva Queiroz, Ubiratan Fabres Machado, Maria Lúcia Correa-Giannella. Variants in HSD11B1 gene modulate susceptibility to diabetes kidney disease and to insulin resistance in type 1 diabetes. Diabetes/metabolism research and reviews. 2021 Jan;37(1):e3352