The R453Q and D151A polymorphisms of hexose-6-phosphate dehydrogenase gene (H6PD) influence the polycystic ovary syndrome (PCOS) and obesity |
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Authors: | Martínez-García M A San-Millán J L Escobar-Morreale H F |
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Institution: | Diabetes, Obesity and Human Reproduction Research Group, Universidad de Alcalá & Hospital Universitario Ramon y Cajal & Instituto Ramón y Cajal de Investigación Sanitaria IRYCIS, 28034 Madrid, Spain. |
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Abstract: | Hexose-6-phosphate dehydrogenase (H6PDH) influences 11β-hydroxysteroid dehydrogenase activity, a key enzyme in the peripheral metabolism of cortisol that modulates insulin sensitivity in adipose tissue. To study the associations of R453Q and D151A polymorphisms in the H6PDH gene (H6PD) with polycystic ovary syndrome (PCOS) and their influence on clinical and metabolic variables, we genotyped 237 patients with PCOS and 135 control women for the R453Q (rs6688832) and D151A (rs34603401) variants in H6PD. The R453Q genotypes were distributed differently in patients and controls (χ(2)=9.55, P=0.002). Genotypes of D151A were distributed evenly in women with PCOS and controls, but showed a different distribution in non-obese and obese women (χ(2)=3.95, P=0.047), especially within the PCOS subgroup (χ(2)=4.65, P=0.031). A backward stepwise likelihood ratio logistic regression model (Nagelkerke's R(2)=0.490; χ(2)=164; P<0.0001) retained free testosterone (OR=1.13; 95% CI: 1.10-1.17) and H6PD Q453 alleles (OR=0.46; 95% CI: 0.27-0.79) as statistically significant predictors for PCOS, whereas homeostasis model assessment of insulin resistance and the H6PD D151A variant were excluded by the model. Both H6PD variants were associated with several phenotypic variables, including fasting insulin, homeostasis model assessment of insulin resistance and androstenedione levels. In summary, the R453Q and D151A variants of the H6PD gene are associated with PCOS and obesity, respectively, and may contribute to the PCOS phenotype by influencing obesity, insulin resistance and hyperandrogenism. |
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Keywords: | 11β-HSD1 11β-hydroxysteroid dehydrogenase BMI body mass index CI confidence interval CRD cortisone reductase deficiency GLM general linear model H6PDH hexose-6-phosphate dehydrogenase H6PD hexose-6-phosphate dehydrogenase HSD11B1 11β-hydroxysteroid dehydrogenase gene OR odds ratio PCOS polycystic ovary syndrome PCR polymerase chain reaction |
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