Sterol 27-Hydroxylase Polymorphism Significantly Associates With Shorter Telomere, Higher Cardiovascular and Type-2 Diabetes Risk in Obese Subjects
Background/objectivesThe pathologic relationship linking obesity and lipid dismetabolism with earlier onset of aging-related disorders, including cardiovascular disease (CVD) and type-2 diabetes (T2D), is not fully elucidate. Chronic inflammatory state, in obese individuals, may accelerate cellular...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2018-06-01
|
| Series: | Frontiers in Endocrinology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fendo.2018.00309/full |
| _version_ | 1819094932787298304 |
|---|---|
| author | Sofia Pavanello Sofia Pavanello Laura Angelici Mirjam Hoxha Laura Cantone Manuela Campisi Amedea Silvia Tirelli Luisella Vigna Angela Cecilia Pesatori Angela Cecilia Pesatori Valentina Bollati Valentina Bollati |
| author_facet | Sofia Pavanello Sofia Pavanello Laura Angelici Mirjam Hoxha Laura Cantone Manuela Campisi Amedea Silvia Tirelli Luisella Vigna Angela Cecilia Pesatori Angela Cecilia Pesatori Valentina Bollati Valentina Bollati |
| author_sort | Sofia Pavanello |
| collection | DOAJ |
| description | Background/objectivesThe pathologic relationship linking obesity and lipid dismetabolism with earlier onset of aging-related disorders, including cardiovascular disease (CVD) and type-2 diabetes (T2D), is not fully elucidate. Chronic inflammatory state, in obese individuals, may accelerate cellular aging. However, leukocyte telomere length (LTL), the cellular biological aging indicator, is elusively linked with obesity. Recent studies indicate that sterol 27-hydroxylase (CYP27A1) is an emerging antiatherogenic enzyme, that, by converting extrahepatic cholesterol to 27-hydroxycholesterol, facilitates cholesterol removal via high-density lipoprotein-cholesterol (HDL-C). We tested the hypothesis that obese subjects who carry at least three copies of CYP27A1 low-hydroxylation (LH) activity genome-wide-validated alleles (rs4674345A, rs1554622A, and rs4674338G) present premature aging, as reflected in shorter LTL and higher levels of CVD/T2D risk factors, including reduced HDL-C.Subjects/methodsObese subjects from SPHERE project {n = 1,457; overweight [body mass index (BMI) 25–30 kg/m2] 65.8% and severe-obese (BMI > 30 kg/m2) 34.2%} were characterized for the presence from 0 to 6 LH-CYP27A1 allele copy number. Univariate and multivariable sex–age–smoking-adjusted linear-regression models were performed to compare CVD/T2D risk factors and biological aging (LTL) in relation to the combined BMI-LH groups: overweight-LH: 0–2, overweight-LH: 3–6, severe-obese-LH: 0–2, and severe-obese-LH: 3–6.ResultsHigher LTL attrition was found in severe-obese than overweight individuals (p < 0.001). Multivariable model reveals that among severe-obese patients those with LH: 3–6 present higher LTL attrition than LH: 0–2 (p < 0.05). Univariate and multivariable models remarkably show that insulin resistance is higher both in overweight-LH: 3–6 vs overweight-LH: 0–2 (p < 0.001) and in severe-obese-LH: 3–6 vs severe-obese-LH: 0–2 (p < 0.0001), and HDL-C is lower in overweight-LH: 3–6 than overweight-LH: 0–2 (p < 0.05 and p < 001). Finally, most of the well-known (i.e., blood pressure, heart rate, waist to hip, triglycerides, and HDL-C) and novel CVD risk factors [i.e., inflammation markers (C-reactive protein, leukocytes, and chemoattractant protein-1), fibrinogen, and glucose homeostasis (i.e., insulin resistance, and glycated hemoglobin)] are substantially (p < 0.0001) altered in severe-obese-LH: 0–2 vs overweight-LH: 0–2, pointing to the fact that obesity leads to worsen the CVD/T2D risk factor profile.ConclusionOur study supports evidence that CYP27A1 genetic characterization identifies persons at higher risk to develop CVD and T2D, on which better converge preventive measures, and opens new perspectives on mechanisms that link obesity with aging-related disorders. |
| first_indexed | 2024-12-21T23:35:16Z |
| format | Article |
| id | doaj.art-7a7db6376b0a46a58710b519f5b9b60d |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-12-21T23:35:16Z |
| publishDate | 2018-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-7a7db6376b0a46a58710b519f5b9b60d2022-12-21T18:46:23ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922018-06-01910.3389/fendo.2018.00309367917Sterol 27-Hydroxylase Polymorphism Significantly Associates With Shorter Telomere, Higher Cardiovascular and Type-2 Diabetes Risk in Obese SubjectsSofia Pavanello0Sofia Pavanello1Laura Angelici2Mirjam Hoxha3Laura Cantone4Manuela Campisi5Amedea Silvia Tirelli6Luisella Vigna7Angela Cecilia Pesatori8Angela Cecilia Pesatori9Valentina Bollati10Valentina Bollati11Medicina del Lavoro, Dipartimento di Scienze Cardiologiche Toraciche e Vascolari, Università di Padova, Padova, ItalyAzienda Ospedaliera di Padova, Unità di Medicina del Lavoro, Padova, ItalyEPIGET – Epidemiology, Epigenetics and Toxicology Laboratory, Dipartimento di Scienze Cliniche e di Comunità, Università degli Studi di Milano, Milan, ItalyEPIGET – Epidemiology, Epigenetics and Toxicology Laboratory, Dipartimento di Scienze Cliniche e di Comunità, Università degli Studi di Milano, Milan, ItalyEPIGET – Epidemiology, Epigenetics and Toxicology Laboratory, Dipartimento di Scienze Cliniche e di Comunità, Università degli Studi di Milano, Milan, ItalyMedicina del Lavoro, Dipartimento di Scienze Cardiologiche Toraciche e Vascolari, Università di Padova, Padova, ItalyDipartimento di Medicina Preventiva, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, ItalyDipartimento di Medicina Preventiva, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, ItalyEPIGET – Epidemiology, Epigenetics and Toxicology Laboratory, Dipartimento di Scienze Cliniche e di Comunità, Università degli Studi di Milano, Milan, ItalyDipartimento di Medicina Preventiva, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, ItalyEPIGET – Epidemiology, Epigenetics and Toxicology Laboratory, Dipartimento di Scienze Cliniche e di Comunità, Università degli Studi di Milano, Milan, ItalyDipartimento di Medicina Preventiva, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, ItalyBackground/objectivesThe pathologic relationship linking obesity and lipid dismetabolism with earlier onset of aging-related disorders, including cardiovascular disease (CVD) and type-2 diabetes (T2D), is not fully elucidate. Chronic inflammatory state, in obese individuals, may accelerate cellular aging. However, leukocyte telomere length (LTL), the cellular biological aging indicator, is elusively linked with obesity. Recent studies indicate that sterol 27-hydroxylase (CYP27A1) is an emerging antiatherogenic enzyme, that, by converting extrahepatic cholesterol to 27-hydroxycholesterol, facilitates cholesterol removal via high-density lipoprotein-cholesterol (HDL-C). We tested the hypothesis that obese subjects who carry at least three copies of CYP27A1 low-hydroxylation (LH) activity genome-wide-validated alleles (rs4674345A, rs1554622A, and rs4674338G) present premature aging, as reflected in shorter LTL and higher levels of CVD/T2D risk factors, including reduced HDL-C.Subjects/methodsObese subjects from SPHERE project {n = 1,457; overweight [body mass index (BMI) 25–30 kg/m2] 65.8% and severe-obese (BMI > 30 kg/m2) 34.2%} were characterized for the presence from 0 to 6 LH-CYP27A1 allele copy number. Univariate and multivariable sex–age–smoking-adjusted linear-regression models were performed to compare CVD/T2D risk factors and biological aging (LTL) in relation to the combined BMI-LH groups: overweight-LH: 0–2, overweight-LH: 3–6, severe-obese-LH: 0–2, and severe-obese-LH: 3–6.ResultsHigher LTL attrition was found in severe-obese than overweight individuals (p < 0.001). Multivariable model reveals that among severe-obese patients those with LH: 3–6 present higher LTL attrition than LH: 0–2 (p < 0.05). Univariate and multivariable models remarkably show that insulin resistance is higher both in overweight-LH: 3–6 vs overweight-LH: 0–2 (p < 0.001) and in severe-obese-LH: 3–6 vs severe-obese-LH: 0–2 (p < 0.0001), and HDL-C is lower in overweight-LH: 3–6 than overweight-LH: 0–2 (p < 0.05 and p < 001). Finally, most of the well-known (i.e., blood pressure, heart rate, waist to hip, triglycerides, and HDL-C) and novel CVD risk factors [i.e., inflammation markers (C-reactive protein, leukocytes, and chemoattractant protein-1), fibrinogen, and glucose homeostasis (i.e., insulin resistance, and glycated hemoglobin)] are substantially (p < 0.0001) altered in severe-obese-LH: 0–2 vs overweight-LH: 0–2, pointing to the fact that obesity leads to worsen the CVD/T2D risk factor profile.ConclusionOur study supports evidence that CYP27A1 genetic characterization identifies persons at higher risk to develop CVD and T2D, on which better converge preventive measures, and opens new perspectives on mechanisms that link obesity with aging-related disorders.https://www.frontiersin.org/article/10.3389/fendo.2018.00309/fullobesitycholesterolHDLgenotypingcardiovascular diseasesdiabetes mellitus type 2 |
| spellingShingle | Sofia Pavanello Sofia Pavanello Laura Angelici Mirjam Hoxha Laura Cantone Manuela Campisi Amedea Silvia Tirelli Luisella Vigna Angela Cecilia Pesatori Angela Cecilia Pesatori Valentina Bollati Valentina Bollati Sterol 27-Hydroxylase Polymorphism Significantly Associates With Shorter Telomere, Higher Cardiovascular and Type-2 Diabetes Risk in Obese Subjects Frontiers in Endocrinology obesity cholesterol HDL genotyping cardiovascular diseases diabetes mellitus type 2 |
| title | Sterol 27-Hydroxylase Polymorphism Significantly Associates With Shorter Telomere, Higher Cardiovascular and Type-2 Diabetes Risk in Obese Subjects |
| title_full | Sterol 27-Hydroxylase Polymorphism Significantly Associates With Shorter Telomere, Higher Cardiovascular and Type-2 Diabetes Risk in Obese Subjects |
| title_fullStr | Sterol 27-Hydroxylase Polymorphism Significantly Associates With Shorter Telomere, Higher Cardiovascular and Type-2 Diabetes Risk in Obese Subjects |
| title_full_unstemmed | Sterol 27-Hydroxylase Polymorphism Significantly Associates With Shorter Telomere, Higher Cardiovascular and Type-2 Diabetes Risk in Obese Subjects |
| title_short | Sterol 27-Hydroxylase Polymorphism Significantly Associates With Shorter Telomere, Higher Cardiovascular and Type-2 Diabetes Risk in Obese Subjects |
| title_sort | sterol 27 hydroxylase polymorphism significantly associates with shorter telomere higher cardiovascular and type 2 diabetes risk in obese subjects |
| topic | obesity cholesterol HDL genotyping cardiovascular diseases diabetes mellitus type 2 |
| url | https://www.frontiersin.org/article/10.3389/fendo.2018.00309/full |
| work_keys_str_mv | AT sofiapavanello sterol27hydroxylasepolymorphismsignificantlyassociateswithshortertelomerehighercardiovascularandtype2diabetesriskinobesesubjects AT sofiapavanello sterol27hydroxylasepolymorphismsignificantlyassociateswithshortertelomerehighercardiovascularandtype2diabetesriskinobesesubjects AT lauraangelici sterol27hydroxylasepolymorphismsignificantlyassociateswithshortertelomerehighercardiovascularandtype2diabetesriskinobesesubjects AT mirjamhoxha sterol27hydroxylasepolymorphismsignificantlyassociateswithshortertelomerehighercardiovascularandtype2diabetesriskinobesesubjects AT lauracantone sterol27hydroxylasepolymorphismsignificantlyassociateswithshortertelomerehighercardiovascularandtype2diabetesriskinobesesubjects AT manuelacampisi sterol27hydroxylasepolymorphismsignificantlyassociateswithshortertelomerehighercardiovascularandtype2diabetesriskinobesesubjects AT amedeasilviatirelli sterol27hydroxylasepolymorphismsignificantlyassociateswithshortertelomerehighercardiovascularandtype2diabetesriskinobesesubjects AT luisellavigna sterol27hydroxylasepolymorphismsignificantlyassociateswithshortertelomerehighercardiovascularandtype2diabetesriskinobesesubjects AT angelaceciliapesatori sterol27hydroxylasepolymorphismsignificantlyassociateswithshortertelomerehighercardiovascularandtype2diabetesriskinobesesubjects AT angelaceciliapesatori sterol27hydroxylasepolymorphismsignificantlyassociateswithshortertelomerehighercardiovascularandtype2diabetesriskinobesesubjects AT valentinabollati sterol27hydroxylasepolymorphismsignificantlyassociateswithshortertelomerehighercardiovascularandtype2diabetesriskinobesesubjects AT valentinabollati sterol27hydroxylasepolymorphismsignificantlyassociateswithshortertelomerehighercardiovascularandtype2diabetesriskinobesesubjects |