Molecular Screening of the 11β‐HSD1 Gene in Men Characterized by the Metabolic Syndrome

Abstract

Adipose tissue type 1 11β‐hydroxysteroid dehydrogenase (11β‐HSD1), which generates hormonally active cortisol from inactive cortisone, has been shown to play a central role in adipocyte differentiation and abdominal obesity‐related metabolic complications. The objective was to investigate whether genetic variations in the human 11β‐HSD1 gene are associated with the metabolic syndrome among French‐Canadian men. We sequenced all exons, the exon‐intron splicing boundaries, and 5′ and 3′ regions of the human 11β‐HSD1 gene in 36 men with the metabolic syndrome, as defined by the National Cholesterol Education Program‐Adult Treatment Panel III, and two controls. Three intronic sequence variants were identified: two single‐nucleotide polymorphisms in intron 3 (g.4478T>G) and intron 4 (g.10733G>C) and one insertion in intron 3 (g.4437‐4438insA). The relative allele frequency was 19.6%, 22.1%, and 19.6% for the g.4478G, g.10733C, and g.4438insA alleles, respectively. One single‐nucleotide polymorphism was identified in exon 6 (c.744G>C or G248G). The frequency of the c.744C allele was only 0.46% in a sample of 217 men. Variants were not associated with components of the metabolic syndrome except for plasma apolipoprotein B levels. In conclusion, molecular screening of the 11β‐HSD1 gene did not reveal any sequence variations that can significantly contribute to the etiology of the metabolic syndrome among French‐Canadians.

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

“…However, several other studies have failed to find evidence of an association between HSD11B1 polymorphisms and type 2 diabetes, obesity, or metabolic syndrome [18][19][20][21].…”

Regulatory Effect of Common Promoter Polymorphisms on the Expression of the <i>11</i>β<i>-Hydroxysteroid Dehydrogenase Type 1 </i>Gene

“…It was also reported that the polymorphism ins4436A in intron 3 was associated with greater body mass, central obesity and insulin resistance in obese Caucasian children [21]. However, there are other studies showing no association between polymorphisms in the HSD11B1 gene and diabetes or obesity in Caucasians [22,23,24]. In our study, we could not find any association between common SNPs of HSD11B1 and type 2 diabetes, although the statistical power for g.+27447G > C and g.+27810C > T was not sufficient to be conclusive of a negative association between these SNPs and type 2 diabetes.…”

“…It was reported that single-nucleotide polymorphisms (SNPs) of the HSD11B1 gene are associated with type 2 diabetes mellitus and insulin resistance in Pima Indians [20] and obesity and insulin resistance in Caucasian children [21]. In contrast, several studies showed no association between polymorphisms of HSD11B1 and body composition or glucose metabolism in Caucasians [22,23,24]. …”

Lack of association of the HSD11B1 gene polymorphisms with obesity and other traits of metabolic syndrome in children and adolescents

“…Therefore, we cannot exclude that the HSD11B1 variants investigated in our study are of no functional significance. As a matter of fact, lack of association between HSD11B1 gene polymorphisms and metabolic complications of obesity was reported in adult populations of French Canadians, Japanese and elderly Dutch [24,35,36]. Still, other gene variants might be implicated in development of MetS traits.…”