HSD11B1 gene polymorphisms in type 2 diabetes and metabolic syndrome—Do we have evidence for the association?

Diabetes mellitus (DM) is a major health problem, and its prevalence has been rapidly increasing in the last century. Being polygenic in nature, multiple genes are involved in developing type 2 diabetes (T2DM). Genes involved in the cortisol pathway interact to develop metabolic syndrome (metS) and T2DM, and these conditions resemble Cushing’s syndrome caused by excess cortisol activity in the visceral adipose tissue. Overexpression of 11β-hydroxysteroid dehydrogenase type 1 enzyme (11β-HSD1), engaged in the inter-conversion of inert cortisone and active cortisol in metabolically active tissues, is associated with insulin resistance (IR), T2DM, hypertension, and metS. Studies have reported the role of single-nucleotide polymorphisms (SNPs) of the HSD11B1 gene in the susceptibility to metS and T2DM. This review offers an overview of the contribution of common HSD11B1 single-nucleotide variants in the development of T2DM and metS. We conducted a literature survey in PubMed, Medline, Google, and Embrase databases with the belief that they may provide a starting point for further dialog or need to conduct further studies in this area. From this review study, the frequently studied SNPs rs12086634 and rs846910 were found to be associated with T2DM and rs12086634, rs1000283, and rs846910 associates with metS. The SNPs rs12086634 and rs846910 show conflicting association with T2DM and metS in various ethnic populations. Further studies with adequate sample size may be needed to confirm the association of HSD11B1 gene polymorphisms in different populations.