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Biomedical subjects

José Sancho

Publications and source records attributed to José Sancho.

17 recordsLinked to original sources
PubMed2006

Effects of thyroid hormones on serum levels of adipokines as studied in patients with differentiated thyroid carcinoma during thyroxine withdrawal.

OBJECTIVE: Previous studies addressing the influence of thyroid hormones on serum levels of adipokines yielded conflicting results. We aimed to study the impact of short-term overt hypothyroidism on serum leptin, resistin, and adiponectin levels in an in vivo human model. DESIGN: Twenty-two women with differentiated thyroid carcinoma were studied the last day of their thyroxine-suppressive treatment, 4-7 days after withdrawal, and the day before whole-body scanning. Evaluations included serum thyroid hormone, leptin, resistin, and adiponectin concentrations, fasting glucose and insulin, lipid profiles, body temperature, body mass index, and total body fat mass. MAIN OUTCOMES: Thyroid function changed from subclinical or mild hyperthyroidism to normal free thyroxine and triiodothyronine levels, ending in overt hypothyroidism. Thyroxine withdrawal resulted in an increase in serum resistin (p = 0.007) and leptin (p = 0.006) concentrations, whereas adiponectin levels remain unchanged. A significant decrease in body temperature during thyroxine withdrawal was paralleled by a decrease in fasting glucose (p = 0.006) and insulin resistance (p = 0.033), which occurred despite an increase in estimated total body fat mass. CONCLUSION: Thyroid hormones are important regulators of energy balance and intermediate metabolism, influencing the serum concentrations of leptin and resistin.

Adiponectin↗
PubMed2005

The polycystic ovary syndrome associated with morbid obesity may resolve after weight loss induced by bariatric surgery.

CONTEXT: The polycystic ovary syndrome (PCOS) is frequently associated with obesity. However, there are very few data about PCOS in morbid obesity, especially with regard to its evolution after bariatric surgery. OBJECTIVE: The objective of this study was to evaluate the response of PCOS to the sustained and marked weight loss achieved by bariatric surgery in morbidly obese women. DESIGN: This was a longitudinal prospective nonrandomized evaluation. SETTINGS: The study was performed at an academic hospital. PATIENTS: Thirty-six consecutive premenopausal women submitted to bariatric surgery were screened for PCOS, which was present in 17. INTERVENTIONS: Bariatric surgery was performed. MAIN OUTCOME MEASURES: Hyperandrogenism, menstrual function, and insulin resistance were estimated before and at least 6 months after bariatric surgery in 12 patients with PCOS. RESULTS: Weight loss (41 +/- 9 kg after 12 +/- 5 months) was paralleled by decreases in the hirsutism score (from 9.5 +/- 6.8 to 4.9 +/- 4.2; P = 0.001), total (69 +/- 32 to 42 +/- 19 ng/dl; P < 0.02) and free testosterone (from 1.6 +/- 0.7 to 0.6 +/- 0.3 ng/dl; P < 0.005), androstenedione (from 4.1 +/- 1.5 to 3.0 +/- 0.9 ng/ml; P < 0.02), and dehydroepiandrosterone sulfate (from 2000 +/- 1125 to 1353 +/- 759 ng/ml; P < 0.005); amelioration of insulin resistance estimated by homeostasis model assessment (from 6.0 +/- 3.0 to 1.6 +/- 1.0; P < 0.001); and restoration of regular menstrual cycles and/or ovulation in all patients. CONCLUSIONS: The PCOS is a frequent finding in women with morbid obesity and may resolve after weight loss induced by bariatric surgery.

Adult↗
PubMed2005

Polymorphisms in the insulin receptor substrate-1 (IRS-1) gene and the insulin receptor substrate-2 (IRS-2) gene influence glucose homeostasis and body mass index in women with polycystic ovary syndrome and non-hyperandrogenic controls.

BACKGROUND: We aimed to evaluate the influence of the Gly972Arg variant of the insulin receptor substrate-1 gene (IRS-1) and the Gly1057Asp variant in IRS-2 on insulin resistance and glucose tolerance in women with polycystic ovary syndrome (PCOS) and healthy controls. METHODS: Genotypes, allelic frequencies, indexes of insulin resistance, glucose tolerance and hormone profiles were studied in a large sample of Spanish PCOS (n = 103) women compared with a control group (n = 48) of healthy women matched for body mass index. RESULTS: No differences in genotype or allelic frequencies were found between PCOS patients and healthy controls. When considering control subjects and PCOS patients as a whole, IRS-1 Arg972 carriers also presented with increased fasting insulin (133 +/- 60 versus 95 +/- 67 pmol/l, P = 0.008) and insulin resistance measured by homeostasis model assessment (4.3 +/- 2.1 versus 3.1 +/- 2.4, P = 0.009) compared with subjects homozygous for Gly972 alleles. These differences were even higher when restricting the analysis to PCOS patients. Subjects homozygous for the Gly1057 allele of IRS-2 presented with increased 60 and 90 min oral glucose tolerance test (OGTT) glucose levels compared with carriers of one or two Asp1057 alleles (7.9 +/- 2.1 versus 7.1 +/- 2.1 mmol/l, P = 0.042 and 7.0 +/- 2.1 versus 6.0 +/- 1.8 mmol/l, P = 0.014), and a similar tendency was observed for 120 min OGTT glucose levels. CONCLUSIONS: The Gly972Arg in IRS-1 and Gly1057Asp in IRS-2 polymorphisms influence glucose homeostasis in premenopausal women, but are not associated with PCOS.

Adult↗
PubMed2005

A study of the hexose-6-phosphate dehydrogenase gene R453Q and 11beta-hydroxysteroid dehydrogenase type 1 gene 83557insA polymorphisms in the polycystic ovary syndrome.

CONTEXT: The R453Q variant in the hexose-6-phosphate dehydrogenase gene (H6PD) and 83557insA mutations in 11beta-hydroxysteroid dehydrogenase (11betaHSD) type 1 gene (HSD11B1) interact, resulting in cortisone reductase deficiency (CRD), a rare disorder characterized by a polycystic ovary syndrome (PCOS)-like phenotype. OBJECTIVE: The objective was to study these mutations in PCOS. DESIGN: The design was a case-control study. SETTING: The study was conducted in an academic hospital. PARTICIPANTS: A total of 116 PCOS patients and 76 nonhyperandrogenic controls participated. MAIN OUTCOME MEASURES: Genotype distributions and influence of genotypes on clinical and biochemical variables and, in 28 patients and 12 controls, estimates of 11betaHSD oxoreductase activity were the main outcome measures. RESULTS: Four controls and five patients presented three of four mutant alleles in H6PD R453Q and HSD11B1 83557insA, which is the genotype observed in some subjects with CRD. Estimates of 11betaHSD oxoreductase activity were measured in six of these nine women, ruling out CRD. Moreover, H6PD R453Q and HSD11B1 83557insA genotypes, either separately or in combination, did not influence 11betaHSD oxoreductase activity. The distribution of H6PD R453Q genotypes (R/R, R/Q, and Q/Q) was different in patients and controls (42% of controls and 63% of PCOS patients were R/R; 53% of controls and 31% of PCOS patients were R/Q; and 5% of controls and 6% of PCOS patients were Q/Q; chi(2) = 9.1; P = 0.011). Patients homozygous for R453 alleles presented with increased cortisol and 17-hydroxyprogesterone levels, compared with carriers of Q453 alleles, but these differences were not observed in controls. On the contrary, HSD11B1 83557insA genotypes were not associated with PCOS and did not influence any phenotypic variable. CONCLUSIONS: Digenic triallelic genotypes of the H6PD R453Q variant and HSD11B1 83557insA mutation do not always cause CRD. On the contrary, the H6PD R453Q variant is associated with PCOS and might influence its phenotype by influencing adrenal activity.

11-beta-Hydroxysteroid Dehydrogenase Type 1↗
PubMed2005

Thyroid hormone replacement therapy in primary hypothyroidism: a randomized trial comparing L-thyroxine plus liothyronine with L-thyroxine alone.

BACKGROUND: Substituting part of the dose of l-thyroxine with small but supraphysiologic doses of liothyronine in hypothyroid patients has yielded conflicting results. OBJECTIVE: To evaluate combinations of L-thyroxine plus liothyronine in hypothyroid patients that match the proportions present in normal secretions of the human thyroid gland. DESIGN: Randomized, double-blind, crossover trial. SETTING: Academic research hospital. PARTICIPANTS: 28 women with overt primary hypothyroidism. INTERVENTION: Crossover trial comparing treatment with l-thyroxine, 100 microg/d (standard treatment), versus treatment with L-thyroxine, 75 microg/d, plus liothyronine, 5 microg/d (combination treatment), for 8-week periods. All patients also received L-thyroxine, 87.5 microg/d, plus liothyronine, 7.5 microg/d (add-on combination treatment), for a final 8-week add-on period. MEASUREMENTS: Primary outcomes included serum thyroid hormone levels, results of quality-of-life and psychometric tests, and patients' preference. Multiple biological thyroid hormone end points were studied as secondary outcomes. RESULTS: Compared with standard treatment, combination treatment led to lower free thyroxine levels (decrease, 3.9 pmol/L [95% CI, 2.5 to 5.3 pmol/L]), slightly higher serum levels of thyroid-stimulating hormone (increase, 0.62 mU/L [CI, 0.01 to 1.23 mU/L]), and unchanged free triiodothyronine levels. No improvement was observed in the other primary and secondary end points after combination treatment, with the exception of the Digit Span Test, in which the mean backward score and the mean total score increased slightly (0.6 digit [CI, 0.1 to 1.0 digit] and 0.8 digit [CI, 0.2 to 1.4 digits], respectively). The add-on combination treatment resulted in overreplacement. Levels of thyroid-stimulating hormone decreased by 0.85 mU/L (CI, 0.27 to 1.43 mU/L) and serum free triiodothyronine levels increased by 0.8 pmol/L (CI, 0.1 to 1.5 pmol/L) compared with standard treatment; 10 patients had levels of thyroid-stimulating hormone that were below the normal range. Twelve patients preferred combination treatment, 6 patients preferred the add-on combination treatment, 2 patients preferred standard treatment, and 6 patients had no preference (P = 0.015). LIMITATIONS: Treatment with L-thyroxine, 87.5 microg/d, plus liothyronine, 7.5 microg/d, was an add-on regimen and was not randomized. CONCLUSIONS: Physiologic combinations of L-thyroxine plus liothyronine do not offer any objective advantage over l-thyroxine alone, yet patients prefer combination treatment.

Adolescent↗
PubMed2005

[Angiosarcoma in an irradiated breast: a case description].

Post-radiotherapy cutaneous angiosarcomas have been described in different locations, including the breast. We present a case of cutaneous angiosarcoma of the breast, diagnosed 6 years after a carcinoma of the breast had been treated with radiation. The patient was a 44-year-old female with a history of ductal carcinoma (CA) of the right breast treated with tumorectomy, axillary lymphadenectomy, chemotherapy (FEC) and radiotherapy, who 6 years later presented with a violaceous, indurated plaque with a satellite nodule on the same breast. The histology of the skin biopsies showed angiomatous proliferation throughout the entire dermis, with no cellular atypia. Considering the patient's symptoms, history and the changes observed via mammography, it was decided to completely excise the lesion followed by a simple mastectomy, with the diagnosis of angiosarcoma being confirmed. The patient was later treated with paclitaxel, and the disease was apparently controlled. Despite this fact, two years and one month later, the angiosarcoma recurred on the internal area of the mastectomy scar. The patient was treated with paclitaxel, and surgical excision of the lesion area was once again performed. This complication usually appears 5-10 years after treatment with radiotherapy, so angiosarcoma should be ruled out if any angiomatous lesions later appear on skin that had been irradiated.

Adult↗
PubMed2005

The effects of thyroid hormones on circulating markers of cell-mediated immune response, as studied in patients with differentiated thyroid carcinoma before and during thyroxine withdrawal.

OBJECTIVE: To address the influence of thyroid hormones on circulating markers of cell-mediated immune response in an in vivo human model. SUBJECTS AND DESIGN: Twenty-two patients with stage I differentiated thyroid carcinoma were studied on the last day of thyroxine suppressive treatment, 4-7 days after withdrawal, and the day before whole body scanning. Three patients were excluded because of residual disease. Twenty euthyroid individuals served as controls. Serum thyrotrophin and thyroid hormones were measured by an immunometric assay, circulating cytokines by enzyme-linked immuno-sorbent assay and lymphoid populations by flow cytometry. RESULTS: Thyroid function in patients changed from subclinical or mild hyperthyroidism at the first visit, to a situation of normal circulating levels of free thyroxine and triiodothyronine at the second, ending in a state of overt hypothyroidism. Thyroxine suppressive treatment in patients increased serum interleukin-18 concentrations (IL-18, mean+/-s.d., 280+/-122 vs 183+/-106 pg/ml, F = 3.192, P = 0.029), soluble interleukin-2 receptor levels (sIL-2R, 4368+/-1480 vs 2564+/-846 pg/ml, F = 21.324, P < 0.001), and the percentage of natural killer (NK) cells in peripheral blood (15.9+/-8.6 vs 10.5+/-3.6%, F = 4.977, P = 0.004) compared with controls. After thyroxine withdrawal, serum levels of IL-18, sIL-2R and the percentage of NK cells decreased progressively. CONCLUSION: Our present results suggest that thyroid hormones modulate the cell-mediated immune response in humans.

Adult↗
PubMed2004

Association of the polycystic ovary syndrome with genomic variants related to insulin resistance, type 2 diabetes mellitus, and obesity.

We have evaluated the possible association of polycystic ovary syndrome (PCOS) with 15 genomic variants previously described to influence insulin resistance, obesity, and/or type 2 diabetes mellitus. Seventy-two PCOS patients and 42 healthy controls were genotyped for 15 variants in the genes encoding for paraoxonase (three variants), plasma cell differentiation antigen glycoprotein, human sorbin and SH3 domain containing 1, plasminogen activator inhibitor-1, peroxisome proliferator-activated receptor-gamma2, protein tyrosine phosphatase 1B (two variants), adiponectin (two variants), IGF1, IGF2, IGF1 receptor, and IGF2 receptor. Compared with controls, PCOS patients were more frequently homozygous for the -108T variant in paraoxonase (36.6% vs. 9.5%; P = 0.002) and homozygous for G alleles of the ApaI variant in IGF2 (62.9% vs. 38.1%; P = 0.018). Paraoxonase is a serum antioxidant enzyme and, because -108T alleles result in decreased paraoxonase expression, this increase in oxidative stress might result in insulin resistance. G alleles of the ApaI variant in IGF2 may increase IGF2 expression, and IGF2 stimulates adrenal and ovarian androgen secretion. In conclusion, the paraoxonase -108 C-->T variant and the ApaI polymorphism in the IGF2 gene are associated with PCOS and might contribute to increased oxidative stress, insulin resistance, and hyperandrogenism in this prevalent disorder.

Adiponectin↗
PubMed2004

Serum interleukin-18 concentrations are increased in the polycystic ovary syndrome: relationship to insulin resistance and to obesity.

Low-grade chronic inflammation is involved in the pathogenesis of the metabolic syndrome and atherosclerosis, and serum levels of inflammatory cytokines are useful cardiovascular risk markers. We have studied serum IL-18 concentrations in women with polycystic ovary syndrome (PCOS), focusing on its relationship with obesity and indexes of insulin resistance. Sixty consecutive women with PCOS and 34 healthy women were recruited. Serum levels of IL-18 and lipid and hormone profiles were measured. The insulin sensitivity index was calculated from glucose and insulin concentrations during an oral glucose tolerance test. Data were submitted to a multivariate general linear model introducing age as a covariate. Serum IL-18 levels were increased in PCOS patients compared with controls (P = 0.031) and in obese women compared with lean women (P = 0.018). No interaction between PCOS and obesity was found, suggesting that the influence of PCOS on serum IL-18 concentrations studied here was not different in lean women compared with obese women and that the influence of obesity on serum IL-18 concentrations was the same in the PCOS and control groups. Serum IL-18 levels correlated, after logarithmic transformation, with body mass index (r = 0.38; P < 0.0002), waist-to-hip ratio (r = 0.33; P < 0.001), and total testosterone levels (r = 0.24; P < 0.02), and inversely with the insulin sensitivity index (r = -0.23; P < 0.03). In conclusion, PCOS and obesity induce an increase in serum IL-18 levels, which are also associated with several indexes of global and visceral adiposity and with insulin resistance.

Adult↗
PubMed2004

Chronic thyrotropin-suppressive therapy with levothyroxine and short-term overt hypothyroidism after thyroxine withdrawal are associated with undesirable cardiovascular effects in patients with differentiated thyroid carcinoma.

To evaluate cardiovascular functionality in patients with thyroid cancer, we have performed echocardiography and ambulatory blood pressure monitoring in 19 women with differentiated thyroid carcinoma during thyroxine withdrawal, at three time points: the last day on TSH-suppressive thyroxine doses (subclinical or mild hyperthyroidism), 4-7 days after withdrawal (normal free thyroxine (FT4) and free triiodothyronine (FT3) levels), and before 131I whole body scanning (overt hypothyroidism). Twenty-one healthy euthyroid women served as controls. When compared with the values at visit 2, when patients had normal serum FT4 and FT3 levels, night-time systolic and mean blood pressure were increased when the patients were mildly hyperthyroid, and night-time systolic, diastolic and mean blood pressure were increased during overt hypothyroidism. The proportion of nondippers (absence of nocturnal decline in blood pressure) was markedly increased compared with healthy controls (7%), when patients were hyper- or hypothyroid (58% and 50% respectively), but not when patients had normal FT4 and FT3 levels (12%). No changes were observed in office blood pressure or in daytime ambulatory blood pressure readings. Diastolic function worsened during thyroxine withdrawal (E and A waves (early and late mitral flow) decreased, and the E/A ratio and the isovolumic relaxation time increased), and cardiac output decreased in parallel with the decrease in heart rate and systolic blood flow. In conclusion, the chronic administration of TSH-suppressive doses of thyroxine and the withdrawal of thyroxine frequently used for the management of differentiated thyroid carcinoma, are associated with undesirable cardiovascular effects.

Adult↗
PubMed2003

Association of polymorphisms in the interleukin 6 receptor complex with obesity and hyperandrogenism.

OBJECTIVE: Interleukin-6 (IL-6), is an inflammatory cytokine that may influence the pathogenesis of obesity and hyperandrogenism. IL-6 exerts its actions through a heterodimeric receptor consisting of two membrane-bound glycoproteins: an 80-kDa IL-6 binding unit (IL6R-alpha) and a 130-kDa IL-6 signal transducer (gp130). Genetic variability at these loci might contribute to explain the development of obesity and hyperandrogenism. RESEARCH METHODS AND PROCEDURES: We have evaluated the possible association of several polymorphisms in the IL6R-alpha and gp130 genes with obesity and/or hyperandrogenism in a case-control study involving 143 hyperandrogenic patients and 45 healthy women from Spain. RESULTS: A microsatellite CA-repeat polymorphism in the IL6R-alpha locus was associated with obesity. The frequency of the common 149-bp allele was markedly increased in obese women compared with controls when considering patients and controls as a whole (0.41 vs. 0.29, chi(2) = 17.085, p < 0.050). On the other hand, the uncommon Arg148 allele of the Gly148Arg polymorphism in the gp130 gene was more frequent in controls compared with hyperandrogenic patients (0.17 vs. 0.08, chi(2) = 5.605, p = 0.026). Controls carrying Arg148 alleles had lower 11-deoxycortisol and 17-hydroxyprogesterone concentrations, a lower response of androstenedione to 1-24 adrenocorticotropin, and an almost significant decrease in free testosterone levels, suggesting that Arg148 alleles in the gp130 gene have a protective effect against androgen excess and adrenal hyperactivity. DISCUSSION: Polymorphisms in the gp130 and IL6R-alpha loci influence hyperandrogenism and obesity, respectively. Our present results further suggest that proinflammatory genotypes are involved in the pathogenesis of these common metabolic disorders.

Adult↗
PubMed2002

[Diagnostic localization of insulinoma and prognostic value of postoperative glycemia monitoring].

BACKGROUND: Our purpose was to establish the efficacy of different diagnostic tests for the diagnosis and localization of insulinoma as well as the prognostic value of postoperative glycemia measurements. PATIENTS AND METHOD: Retrospective analysis of all insulinoma patients diagnosed at our hospital over the last fifteen years. Every patient underwent a supervised prolonged fasting and localization imaging tests were performed in positive cases. In the immediate preoperative period, during surgical intervention and immediately after it, an intravenous dextrose solution (10% concentration, 2-3 g/Kg/d infusion rate) was used to avoid hypoglycemia. Glycemia was measured every 6-8 h from the immediate postoperative period until hospital discharge. RESULTS: Seventeen insulinoma cases were identified (incidence 2.5 cases/million/year), 59% women and 41% men. The sensitivity (and positive predictive value) of diagnostic tests was: conventional-contrast CT scan 30% (75%), spiral CT scan 71.42% (100%), arteriography 28.57% (100%) and intraoperative ultrasonography 100% (100%). MRI identified insulinoma in two out of five patients and In-pentetreotide scintigraphy only in one out of five. Patients subsequently developing diabetes mellitus or glucose intolerance had higher levels of postoperative glycemia, which also lasted for more days, and longer need for insulin therapy. However, patients with a recurrence of the tumor did not show rebound hyperglycemia at all. CONCLUSION: Postoperative glycemia could be a useful prognostic factor in patients who develop diabetes mellitus or glucose intolerance after resection of insulinoma and to predict insulinoma recurrence.

Blood Glucose↗
PubMed2002

Common single nucleotide polymorphisms in intron 3 of the calpain-10 gene influence hirsutism.

OBJECTIVE: To study three common polymorphisms in intron 3 of the calpain-10 gene (CAPN10) in hyperandrogenic patients. DESIGN: Case-control study. SETTING: Academic hospital. PATIENT(S): Ninety-seven hyperandrogenic patients and 37 healthy controls. INTERVENTION(S): Basal and adrenocorticotropin-stimulated serum samples and genomic DNA samples were obtained during the follicular phase of the menstrual cycle. MAIN OUTCOME MEASURE(S): Genotyping of the UCSNP43, UCSNP44, and UCSNP45 polymorphisms in CAPN10 and serum androgen levels. RESULT(S): Sixteen patients had idiopathic hirsutism, defined as normal serum androgen levels and regular menstrual cycles. Eighty-one hyperandrogenic patients (those presenting with hyperandrogenemic hirsutism or the polycystic ovary syndrome) were analyzed further. UCSNP45 alleles were distributed differently among the study groups. Heterozygosity for the uncommon C allele was increased in patients with idiopathic hirsutism (31.3%) and reduced in hyperandrogenic patients (7.4%) compared with controls (16.2%). The UCSNP44 and UCSNP43 alleles were in linkage disequilibrium, and were distributed equally among patients with idiopathic hirsutism, hyperandrogenism, and controls. However, the uncommon A allele at UCSNP43 was associated with higher hirsutism score (mean [+/- SD], 9.9 +/- 6.8, 12.7 +/- 7.7, and 14.6 +/- 8.2 in GG, GA, and AA participants, respectively). No other differences were observed in clinical and biochemical characteristics, including insulin sensitivity, by CAPN10 variant. CONCLUSION(S): The C allele at the UCSNP45 locus in CAPN10 is associated with idiopathic hirsutism, and UCSNP43 influences the hirsutism score.

17-alpha-Hydroxyprogesterone↗
PubMed2002

Insulin gene variable number of tandem repeats regulatory polymorphism is not associated with hyperandrogenism in Spanish women.

OBJECTIVE: To determine if the insulin gene variable number of tandem repeats (VNTR) regulatory polymorphism is associated with hyperandrogenism in a population of Spanish women. DESIGN: Controlled clinical study. SETTING: Tertiary institutional hospital. PATIENT(S): Ninety-six hyperandrogenic patients and 38 healthy control women. INTERVENTION(S): Whole blood and serum samples were collected during the follicular phase of the menstrual cycle. MAIN OUTCOME MEASURE(S): Insulin gene VNTR regulatory polymorphism genotypes (classes I/I, I/III, and III/III alleles) and serum androgen levels. Insulin resistance was estimated from fasting glucose and insulin levels by using the homeostatic model assessment. RESULT(S): The frequencies of VNTR genotypes were 45.5%, 43.3%, and 11.2% for I/I, I/III, and III/III alleles considering patients and controls as a whole. These frequencies were not statistically different in controls (47.4%, 34.2%, and 18.4%) and in patients (44.8%, 46.9%, and 8.3%). CONCLUSION(S): Hyperandrogenism and the insulin gene VNTR regulatory polymorphism are not associated in Spanish women.

17-alpha-Hydroxyprogesterone↗
PubMed2002

The -597 G-->A and -174 G-->C polymorphisms in the promoter of the IL-6 gene are associated with hyperandrogenism.

To evaluate whether genetic variability at the IL-6 gene (IL-6) is associated with hyperandrogenism, we studied four common polymorphisms in the IL-6 promoter (-597G-->A, -572G--> C, -373A(n)T(n), -174G-->C) in 85 hyperandrogenic patients and 25 healthy women. We found 5 different haplotypes when considering the 3 biallelic polymorphisms at positions -597, -572, and -174 of IL-6 (relative frequencies in parentheses): GGG (0.505), AGC (0.377), GGC (0.059), GCG (0.055), and GCC (0.005). The frequencies of the GGG haplotype were 0.559 in patients and 0.320 in controls, whereas those of the AGC haplotype were 0.318 in patients and 0.580 in controls (chi(2) = 12.145; P < 0.02). The -597G-->A and -174G-->C polymorphisms were in linkage disequilibrium (chi(2) = 152.220; P < 0.00001), and were associated with patient or control status. -597G and -174G alleles were more frequent in patients in homozygosity or considering subjects homozygous and heterozygous for G alleles as a whole (P < 0.05 for all analyses). In healthy women G alleles at -597 and -174 were associated with statistically significant higher circulating levels of IL-6 and basal cortisol, 11-deoxycortisol, and 17-hydroxyprogesterone and a tendency (P < 0.10) for higher total T concentrations compared with -597A and -174C alleles. On the contrary, neither the -572G-->C nor the -373A(n)T(n) polymorphism was related to hyperandrogenism or influenced any clinical or biochemical variable. In conclusion, our present results suggest that the -597G-->A and -174G-->C polymorphisms in IL-6 are involved in the pathogenesis of hyperandrogenic disorders.

Adult↗