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The  HSD11B1  gene is highly expressed in abdominal adipose tissue, and the enzyme it encodes catalyzes the interconversion of inactive cortisone to hormonally active cortisol. Genetic abnormalities of  HSD11B1  have been associated with the development of abnormal glucose metabolism and body fat distribution. To systematically review studies evaluating the association of  HSD11B1  gene expression in abdominal adipose tissue and  HSD11B1  polymorphisms with obesity, the metabolic syndrome (MetS), and type 2 diabetes (T2DM), we conducted a search in MEDLINE, SCOPUS, and Cochrane Library databases in April 2015. The inclusion criteria were observational studies (cross-sectional, cohort, or case–control), conducted in adults, which analyzed the relationship of  HSD11B1  polymorphisms and/or  HSD11B1  expression in abdominal adipose tissue with obesity, MetS, or T2DM. Of 802 studies retrieved, 32 met the inclusion criteria (23 gene expression and 9 polymorphism studies). Twenty one studies analyzed the relationship between abdominal subcutaneous and/or visceral  HSD11B1  expression with central and/or generalized obesity. Most studies reported that abdominal adipose  HSD11B1  expression increased with increasing body mass index (15 studies) and abnormalities of glucose metabolism (7 studies), and varied with the presence of MetS (3 studies). Nine studies analyzed the association of 26 different  HSD11B1  polymorphic variants with obesity, MetS, and T2DM. Only an Indian study found an association between a polymorphic variant at the  HSD11B1  gene with MetS whereas in Pima Indians another polymorphic variant was found to be associated with T2DM. While the literature suggests that  HSD11B1  is hyperexpressed in abdominal adipose tissue in subjects with obesity and abnormal glucose metabolism, this seems to be not true for  HSD11B1  gene expression and MetS. Although an association of polymorphic variants of  HSD11B1  with MetS in Indians and in the T2DM population of Pima Indians were found, most studies did not find a relationship between genetic polymorphic variants of  HSD11B1  and obesity, MetS, and T2DM. Their reported conflicting and inconclusive results, suggesting that polymorphic variants of HSD11B1 may have only a small role in the development of metabolic abnormalities of susceptible populations in the development of MetS and T2DM.

diabetology and metabolic syndrome

Association of HSD11B1 polymorphic variants and adipose tissue gene expression with metabolic syndrome, obesity and type 2 diabetes mellitus: a systematic review