Association of TLR2 S450S and ICAM1 K469E polymorphisms with polycystic ovary syndrome (PCOS) and obesity.
Toll-like receptors (TLRs) are activated by inflammatory stimuli and influence endothelial functions, contributing to the pathogenesis of atherosclerosis. We investigate the influence of polymorphisms in the genes encoding toll-like receptor 2 (TLR2) and 4 (TLR4) and endothelial adhesion molecules on polycystic ovary syndrome (PCOS) and its interaction with obesity. Ten single nucleotide polymorphisms were genotyped in 305 women with PCOS and 166 non-hyperandrogenic control women. In obese women, TLR2 S450S and ICAM1 K469E polymorphisms differently influenced metabolic variables and PCOS, respectively. Irrespective of PCOS, variant alleles of TLR2 S450S increased triglycerides, fasting insulin levels, and insulin resistance in obese women. TLR2 S450S interacted with obesity and PCOS on androstenedione levels, mutant alleles were associated with increased androstenedione concentrations in all women, with the exception of obese patients with PCOS (P=0.034). Regarding ICAM1 K469E, homozygosis for K469 alleles was more frequent in PCOS, but only in obese women (P=0.014). K469 alleles were also related to increased body mass index (P=0.017) and diastolic blood pressure (P=0.034). Moreover, ICAM1 K469E interacted with obesity and PCOS on serum triglyceride levels (P=0.019) and with PCOS on serum sex hormone-binding globulin concentrations (P=0.006). In conclusion, TLR2 S450S and ICAM1 K469E polymorphisms may be associated with PCOS and metabolic comorbidities in obese women.
Diabetes, Obesity and Human Reproduction Research Group, Department of Endocrinology & Nutrition, Hospital Universitario Ramón y Cajal & Universidad de Alcalá & Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS) E-28034 Madrid, Spain & Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Spain. Electronic address: ojedaojedamiriam@gmail.com.
Miriam
M
Ojeda-Ojeda
Diabetes, Obesity and Human Reproduction Research Group, Department of Endocrinology & Nutrition, Hospital Universitario Ramón y Cajal & Universidad de Alcalá & Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS) E-28034 Madrid, Spain & Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Spain.
M Ángeles
MÁ
Martínez-García
Diabetes, Obesity and Human Reproduction Research Group, Department of Endocrinology & Nutrition, Hospital Universitario Ramón y Cajal & Universidad de Alcalá & Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS) E-28034 Madrid, Spain & Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Spain.
Macarena
M
Alpañés
Diabetes, Obesity and Human Reproduction Research Group, Department of Endocrinology & Nutrition, Hospital Universitario Ramón y Cajal & Universidad de Alcalá & Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS) E-28034 Madrid, Spain & Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Spain.
Manuel
M
Luque-Ramírez
Diabetes, Obesity and Human Reproduction Research Group, Department of Endocrinology & Nutrition, Hospital Universitario Ramón y Cajal & Universidad de Alcalá & Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS) E-28034 Madrid, Spain & Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Spain. Electronic address: hectorfrancisco.escobar@salud.madrid.org.
Héctor F
HF
Escobar-Morreale
D000328:Adult; D000483:Alleles; D019943:Amino Acid Substitution; D000735:Androstenedione / Q000097:blood / Q000235:genetics / Q000276:immunology; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood / Q000235:genetics / Q000276:immunology; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood / Q000235:genetics / Q000276:immunology*; D009765:Obesity / Q000097:blood / Q000150:complications / Q000235:genetics* / Q000276:immunology; D011085:Polycystic Ovary Syndrome / Q000097:blood / Q000150:complications / Q000235:genetics* / Q000276:immunology; D011110:Polymorphism, Genetic; D051195:Toll-Like Receptor 2 / Q000097:blood / Q000235:genetics* / Q000276:immunology; D014280:Triglycerides / Q000097:blood / Q000235:genetics / Q000276:immunology
C573420:ICAM1 protein, human; D007328:Insulin; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D014280:Triglycerides; D018799:Intercellular Adhesion Molecule-1; D000735:Androstenedione
Androgen excess; Endothelial dysfunction; Inflammation; Innate immunity; Obesity; Polycystic ovary syndrome; Toll-like receptors