Citosine-Adenine-Repeat Microsatellite of 11β-hydroxysteroid dehydrogenase 2 Gene in Hypertensive Children

Abstract

Background: The impairment of 11β-hydroxysteroid dehydrogenase type 2 enzyme (11βHSD2) results in an inefficient conversion of cortisol to cortisone, which triggers hypertension. Cytosine-adenine repeat (CA repeat) microsatellite has been associated with low HSD11B2 gene expression.

Aim: To determine whether the CA-repeat length in intron 1 affect the serum cortisol to cortisone (F/E) ratio and/or blood pressure (BP) levels in pediatric subjects.

Subjects and methods: Eighty-one hypertensive (HT) and 117 normotensive (NT) subjects participated in this study. We measured BP levels, as well as the F and E and F/E ratio in morning sera and 12-hour urine samples. The length of CA repeats was determined through fragment analysis. We compared the allele distribution between the HT and NT groups, and the patients were dichotomized into groups with short alleles (S) (<21 CA repeats) or long alleles (L), and also in groups according genotype (allele combination: S/S and S/L + L/L).

Results: We found no differences in the distribution of CA-repeat allelic length between the NT and HT groups (P = 0.7807), and there was no correlation between the CA-repeat allelic length and BP (P = 0.1151) levels or the serum F/E ratio (P = 0.6778). However, the serum F/E ratio was higher in the HT group than in the NT group (P = 0.0251). The serum F/E ratio was associated with systolic BP index independent of body mass index only in HT group.

Conclusions: The CA-repeat length did not influence BP levels or serum F/E ratios in pediatric subjects. However, the serum F/E ratio was associated with BP, suggesting a role of 11βHSD2 in mineralocorticoid hypertension.

Keywords: 11βHSD2; CA repeat; HSD11B2; arterial hypertension; blood pressure; hypertension; microsatellite region; short tandem repeat (STR).