• PMID: 16551740
• Gene Name: AGFG1
• Condition: Globozoospermia, male infertility
• Association: Associated
• Mutation: Hrb (19081 A DEL, 39 T/C: V139A, 751 T/C (rs7588620), 38 A/G: T472T (rs13426422), 538 A/G (rs13382948)), Csnk2a2 (509 A/G (rs16959755), 839 T/C, 919 A/G (rs2242444), 410 C/A (rs2242445)), GOPC (509 A/G, 531 T/G, 556 C/T, 445 G/A, 612 G/A)
• Population size: 10
• Population details: 10 (Family1: 1 primary infertility, I globozoospermia, 5 fertile, Family 2: 1 primary infertility, I globozoospermia, 1 fertile)
• Age: Patient1: 42-years, Patient2: 36-years
• Sex: Male
• Infertility type: Male infertility
• Associated genes: Hrb, GOPC, Csnk2a2
• Other associated phenotypes: Globozoospermia, male infertility

Genetic variation in 11beta-hydroxysteroid dehydrogenase type 1 predicts adrenal hyperandrogenism among lean women with polycystic ovary syndrome

Gambineri A, Vicennati V, Genghini S, Tomassoni F, Pagotto U, Pasquali R, Walker BR.

CONTEXT: Elevated adrenal androgen levels are common in polycystic ovary syndrome (PCOS), but the underlying pathogenetic mechanism is poorly understood. In the rare cortisone reductase deficiency, impaired regeneration of active cortisol from inert cortisone by 11beta-hydroxysteroid dehydrogenase (11beta-HSD1) results in compensatory activation of ACTH secretion and adrenal hyperandrogenism. 11beta-HSD1 deficiency may protect against obesity and its metabolic consequences because of impaired regeneration of cortisol in adipose tissue. OBJECTIVE: Our objective was to investigate a functional polymorphism in HSD11B1 (T-->G in the third intron rs12086634, which associates with lower 11beta-HSD1 activity) in PCOS with and without obesity. DESIGN AND SETTING: We conducted a case-control study in lean and obese PCOS patients and controls at an academic hospital. PARTICIPANTS: Participants included 102 Caucasian PCOS patients and 98 controls comparable for age, weight, and race. MAIN OUTCOME MEASURES: We assessed genotype distribution and influence of genotypes on clinical, hormonal, and metabolic parameters. RESULTS: The G allele was significantly related to PCOS status (P = 0.041), and this association was mainly attributable to lean (P = 0.025), rather than obese (P = 0.424), PCOS patients. The G allele was associated with lower 0800-0830 h plasma cortisol (P < 0.001) and higher cortisol response to ACTH(1-24) (P < 0.001) in all women with PCOS and with higher dehydroepiandrosterone sulfate levels (P < 0.001), greater suppression of dehydroepiandrosterone sulfate by dexamethasone (P < 0.001), and lower fasting plasma low-density lipoprotein cholesterol (P = 0.002) levels in lean PCOS women. CONCLUSIONS: Genetic variation in 11beta-HSD1 contributes to enhanced cortisol clearance and compensatory adrenal hyperandrogenism in lean patients with PCOS but may be protective against obesity and some features of the metabolic syndrome. FAU - Gambineri, Alessandra AU - Gambineri A AD - Division of Endocrinology, Department of Internal Medicine, S. Orsola-Malpighi Hospital, via Massarenti 9, 40138 Bologna, Italy. gambineri@aosp.bo.it FAU - Vicennati, Valentina AU - Vicennati V FAU - Genghini, Silvia AU - Genghini S FAU - Tomassoni, Federica AU - Tomassoni F FAU - Pagotto, Uberto AU - Pagotto U FAU - Pasquali, Renato AU - Pasquali R