Molecular screening of the 11β-HSD1 gene in men characterized by the metabolic syndrome

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.