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11β-Hydroxysteroid dehydrogenase type 1 (HSD11B1), which converts inactive glucocorticoid to active glucocorticoid, plays a critical role in the pathogenesis of visceral obesity, metabolic syndrome, and diabetes.  Hexose-6-phosphate dehydrogenase (H6PD) supplies a crucial cofactor, reduced nicotinamide adenine dinucleotide phosphate (NADPH), which allows HSD11B1 to maintain reductase activity.  The association of common SNPs in HSD11B1 [IVS3-29G/T (rs12086634), IVS4-11120A/G (rs1000283)] and H6PD [R453Q (rs6688832), P554L (rs17368528)], either separately or combined, with type 2 diabetes and metabolic syndrome was examined in 427 Korean subjects with type 2 diabetes and in 358 nondiabetic Korean subjects.  HSD11B1 polymorphisms (rs12086634 and rs1000283) were associated with metabolic syndrome among type 2 diabetic subjects and an H6PD polymorphism (rs17368528) was a risk factor for metabolic syndrome in nondiabetic subjects.  However, no significant association of these SNPs with type 2 diabetes and metabolic syndrome was found after considering the multiple comparisons in the total study population.  In conclusion, HSD11B1 and H6PD polymorphisms may not be associated with type 2 diabetes and metabolic syndrome.  Further investigation of the role of these gene polymorphisms on the pathogenesis of metabolic syndrome is required.

endocrine journal

Relationship of 11.BETA.-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase gene polymorphisms with metabolic syndrome and type 2 diabetes