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Article ; Online: Menopause modulates the association between thyrotropin levels and lipid parameters: The SardiNIA study.

Delitala, Alessandro P / Steri, Maristella / Pilia, Maria Grazia / Dei, Mariano / Lai, Sandra / Delitala, Giuseppe / Schlessinger, David / Cucca, Francesco

Maturitas

2016 Volume 92, Page(s) 30–34

Abstract: Objective: Thyroid hormone influences lipoprotein metabolism. The role of menopausal status in this association has not been extensively studied. The aim of the present study is to evaluate the association between lipid parameters and mild elevations of ...

Abstract	Objective: Thyroid hormone influences lipoprotein metabolism. The role of menopausal status in this association has not been extensively studied. The aim of the present study is to evaluate the association between lipid parameters and mild elevations of thyrotropin (TSH), and whether menopause influences this relationship. Study design: A cross-sectional study was conducted with a sample of 2,914 women (aged 14-102 years) from the SardiNIA study. Main outcome measures: The association of TSH with blood lipid levels was examined using regression analyses, according to menopausal status. Results: Postmenopausal women had lower serum TSH concentrations and higher levels of total cholesterol, low-density lipoprotein cholesterol (LDLc), high-density lipoprotein cholesterol (HDLc), and triglycerides than did premenopausal women (p=0.001 or less for all). In premenopausal women, after adjusting for the confounders age, BMI, smoking, insulin and glycaemia, TSH showed a direct relation to the levels of total cholesterol (β=0.046, p=0.010), LDLc (β=0.044, p=0.016) and triglycerides (β=0.085, p<0.001), but no association with HDLc level. In the postmenopausal group, TSH was directly associated only with triglyceride levels (β=0.103, p=0.014). Conclusions: The association between mild elevation of TSH and lipid levels is influenced by menopausal status. Further research is needed to clarify this finding.
MeSH term(s)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; Cholesterol/blood ; Cholesterol, HDL/blood ; Cholesterol, LDL/blood ; Cross-Sectional Studies ; Female ; Humans ; Insulin/blood ; Italy ; Lipids/blood ; Menopause/blood ; Middle Aged ; Smoking/blood ; Thyrotropin/blood ; Triglycerides/blood ; Young Adult
Chemical Substances	Cholesterol, HDL ; Cholesterol, LDL ; Insulin ; Lipids ; Triglycerides ; Thyrotropin (9002-71-5) ; Cholesterol (97C5T2UQ7J)
Language	English
Publishing date	2016-07-14
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	80460-5
ISSN	1873-4111 ; 0378-5122
ISSN (online)	1873-4111
ISSN	0378-5122
DOI	10.1016/j.maturitas.2016.07.003
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Zs.A 1432: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 575: Show issues

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Article ; Online: Prevalence of unknown thyroid disorders in a Sardinian cohort.

Delitala, Alessandro P / Pilia, Maria Grazia / Ferreli, Liana / Loi, Francesco / Curreli, Nicolò / Balaci, Lenuta / Schlessinger, David / Cucca, Francesco

European journal of endocrinology

2014 Volume 171, Issue 1, Page(s) 143–149

Abstract: Objective: To assess thyroid function, the presence of thyroid antibodies, as well as the presence of goiter and/or nodules in subjects without a prior diagnosis of thyroid disorders, in a region with mild to moderate iodine deficiency.: Design and ... ...

Abstract	Objective: To assess thyroid function, the presence of thyroid antibodies, as well as the presence of goiter and/or nodules in subjects without a prior diagnosis of thyroid disorders, in a region with mild to moderate iodine deficiency. Design and methods: This cross-sectional study is based on data obtained from first and third visits of participants in the Sardinian survey. We performed two different analyses. In one, we assessed the prevalence of unknown thyroid dysfunctions among 6252 subjects who had a medical examination and blood collection for assays of thyrotropin, free thyroxine, and antibodies against thyroperoxidase (AbTPO) and against thyroglobulin (AbTG). In a second analysis, we evaluated the frequency of undiagnosed goiter and nodules among 3377 subjects who had a thyroid ultrasound scan. Subjects were excluded if they had a previous history of thyroid disorders or presence of goiter and/or nodules, or thyroid surgery, or if they were taking drugs that could impair thyroid function. Results: We found a low prevalence of overt thyroid dysfunction (hyperthyroidism 0.4% and hypothyroidism 0.7%). The rates of subclinical hypothyroidism and hyperthyroidism were 4.7 and 2.4% respectively. Almost 16% of participants were positive for at least one antibody and 5.2% for both AbTG and AbTPO. Nodules were detected in 17.4% of subjects and the prevalence of goiter was 22.1%. Conclusions: Undiagnosed biochemical thyroid dysfunctions, unknown nodules, and goiter were common in subjects living in a mild to moderate iodine-deficient area. In this community, thyroid disorders often go undetected and screening could be reasonable in subjects at a higher risk.
MeSH term(s)	Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Cross-Sectional Studies ; Humans ; Iodide Peroxidase/metabolism ; Middle Aged ; Thyroglobulin/metabolism ; Thyroid Diseases/diagnosis ; Thyroid Diseases/epidemiology ; Thyroid Diseases/metabolism ; Thyroid Gland/metabolism ; Thyroxine/metabolism
Chemical Substances	Thyroglobulin (9010-34-8) ; Iodide Peroxidase (EC 1.11.1.8) ; Thyroxine (Q51BO43MG4)
Language	English
Publishing date	2014-06-12
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1183856-5
ISSN	1479-683X ; 0804-4643
ISSN (online)	1479-683X
ISSN	0804-4643
DOI	10.1530/EJE-14-0182
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Article ; Online: Gender specific profiles of white coat and masked hypertension impacts on arterial structure and function in the SardiNIA study.

Scuteri, Angelo / Morrell, Christopher H / Orru', Marco / AlGhatrif, Majid / Saba, Pier Sergio / Terracciano, Antonio / Ferreli, Liana Anna Pina / Loi, Francesco / Marongiu, Michele / Pilia, Maria Grazia / Delitala, Alessandro / Tarasov, Kirill V / Schlessinger, David / Ganau, Antonello / Cucca, Francesco / Lakatta, Edward G

International journal of cardiology

2016 Volume 217, Page(s) 92–98

MeSH term(s)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; Aging/physiology ; Blood Pressure Monitoring, Ambulatory/methods ; Female ; Health Surveys ; Humans ; Italy/epidemiology ; Male ; Masked Hypertension/epidemiology ; Middle Aged ; Prevalence ; Prospective Studies ; Sex Characteristics ; White Coat Hypertension/epidemiology ; Young Adult
Language	English
Publishing date	2016-05-03
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	779519-1
ISSN	1874-1754 ; 0167-5273
ISSN (online)	1874-1754
ISSN	0167-5273
DOI	10.1016/j.ijcard.2016.04.172
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Article ; Online: Longitudinal perspective on the conundrum of central arterial stiffness, blood pressure, and aging.

Scuteri, Angelo / Morrell, Christopher H / Orrù, Marco / Strait, James B / Tarasov, Kirill V / Ferreli, Liana Anna Pina / Loi, Francesco / Pilia, Maria Grazia / Delitala, Alessandro / Spurgeon, Harold / Najjar, Samer S / AlGhatrif, Majd / Lakatta, Edward G

Hypertension (Dallas, Tex. : 1979)

2014 Volume 64, Issue 6, Page(s) 1219–1227

Abstract: The age-associated increase in arterial stiffness has long been considered to parallel or to cause the age-associated increase in blood pressure (BP). Yet, the rates at which pulse wave velocity (PWV), a measure of arterial stiffness, and BP trajectories ...

Abstract	The age-associated increase in arterial stiffness has long been considered to parallel or to cause the age-associated increase in blood pressure (BP). Yet, the rates at which pulse wave velocity (PWV), a measure of arterial stiffness, and BP trajectories change over time within individuals who differ by age and sex have not been assessed and compared. This study determined the evolution of BP and aortic PWV trajectories during a 9.4-year follow-up in >4000 community-dwelling men and women of 20 to 100 years of age at entry into the SardiNIA Study. Linear mixed effects model analyses revealed that PWV accelerates with time during the observation period, at about the same rate over the entire age range in both men and women. In men, the longitudinal rate at which BP changed over time, however, did not generally parallel that of PWV acceleration: at ages>40 years the rates of change in systolic BP (SBP) and pulse pressure (PP) increase plateaued and then declined so that SBP, itself, also declined at older ages, whereas PP plateaued. In women, SBP, diastolic BP, and mean BP increased at constant rates across all ages, producing an increasing rate of increase in PP. Therefore, increased aortic stiffness is implicated in the age-associated increase in SBP and PP. These findings indicate that PWV is not a surrogate for BP and that arterial properties other than arterial wall stiffness that vary by age and sex also modulate the BP trajectories during aging and lead to the dissociation of PWV, PP, and SBP trajectories in men.
MeSH term(s)	Adult ; Age Distribution ; Age Factors ; Aged ; Aged, 80 and over ; Aging ; Blood Pressure/physiology ; Disease Progression ; Female ; Follow-Up Studies ; Humans ; Hypertension/epidemiology ; Hypertension/physiopathology ; Incidence ; Italy/epidemiology ; Male ; Middle Aged ; Vascular Stiffness/physiology ; Young Adult
Language	English
Publishing date	2014-09-15
Publishing country	United States
Document type	Journal Article ; Multicenter Study ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural
ZDB-ID	423736-5
ISSN	1524-4563 ; 0194-911X ; 0362-4323
ISSN (online)	1524-4563
ISSN	0194-911X ; 0362-4323
DOI	10.1161/HYPERTENSIONAHA.114.04127
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Zs.A 1488: Show issues

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Article ; Online: Personality traits and circadian blood pressure patterns: a 7-year prospective study.

Terracciano, Antonio / Strait, James / Scuteri, Angelo / Meirelles, Osorio / Sutin, Angelina R / Tarasov, Kirill / Ding, Jun / Marongiu, Michele / Orru, Marco / Pilia, Maria Grazia / Cucca, Francesco / Lakatta, Edward / Schlessinger, David

Psychosomatic medicine

2014 Volume 76, Issue 3, Page(s) 237–243

Abstract: Objective: A nighttime dip in blood pressure is associated with decreased risk of cardiovascular morbidity and mortality. We examined whether personality traits predict nighttime dipping blood pressure.: Methods: A community-based sample of 2848 ... ...

Abstract	Objective: A nighttime dip in blood pressure is associated with decreased risk of cardiovascular morbidity and mortality. We examined whether personality traits predict nighttime dipping blood pressure. Methods: A community-based sample of 2848 adults from Sardinia (Italy) completed the Revised NEO Personality Inventory and 7 years later were examined with 24-hour ambulatory blood pressure monitoring. The primary analyses examined the associations of personality traits with continuous and categorical measures of mean arterial, systolic, and diastolic blood pressure nighttime dipping. Results: Agreeableness and conscientiousness were associated with more nocturnal blood pressure dipping (β = .05 [p = .025] and β = .07 [p < .001], respectively) and lower systolic blood pressure at night (β = -.05 [p = .018] and β = -.03 [p = .072], respectively). Nondippers were particularly more impulsive (p = .009), less trusting (p = .004), and less self-disciplined (p = .001), but there was no significant association between nocturnal dipping blood pressure and trait anxiety (p = .78) or depression (p = .59). The associations were stronger when comparing extreme dippers (nighttime drop ≥ 20%) to reverse dippers (nighttime increase in blood pressure). Indeed, scoring 1 standard deviation higher on conscientiousness was associated with approximately 40% reduced risk of reverse dipping (odds ratio = 1.43, confidence interval = 1.08-1.91). Conclusions: We found evidence that reduced nighttime blood pressure dipping is associated with antagonism and impulsivity-related traits but not with measures of emotional vulnerability. The strongest associations were found with conscientiousness, a trait that may have a broad impact on cardiovascular health.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Blood Pressure/physiology ; Blood Pressure Monitoring, Ambulatory/statistics & numerical data ; Cardiovascular Diseases/epidemiology ; Circadian Rhythm/physiology ; Female ; Humans ; Impulsive Behavior ; Italy ; Logistic Models ; Male ; Middle Aged ; Odds Ratio ; Personality/classification ; Personality/physiology ; Personality Inventory ; Prospective Studies ; Risk Factors ; Trust ; Young Adult
Language	English
Publishing date	2014-03-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural
ZDB-ID	3469-1
ISSN	1534-7796 ; 0033-3174
ISSN (online)	1534-7796
ISSN	0033-3174
DOI	10.1097/PSY.0000000000000035
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Article ; Online: Are personality traits associated with white-coat and masked hypertension?

Terracciano, Antonio / Scuteri, Angelo / Strait, James / Sutin, Angelina R / Meirelles, Osorio / Marongiu, Michele / Orru, Marco / Pilia, Maria Grazia / Ferrucci, Luigi / Cucca, Francesco / Schlessinger, David / Lakatta, Edward

Journal of hypertension

2014 Volume 32, Issue 10, Page(s) 1987–92; discussion 1992

Abstract: Objectives: Anxiety and other psychological dispositions are thought to be associated with blood pressure. This study tests whether personality traits have long-term associations with masked and white-coat effects.: Methods: A community-based sample ... ...

Abstract	Objectives: Anxiety and other psychological dispositions are thought to be associated with blood pressure. This study tests whether personality traits have long-term associations with masked and white-coat effects. Methods: A community-based sample of 2838 adults from Sardinia (Italy) completed the Revised NEO Personality Inventory, and 7 years later, blood pressure was assessed in the clinic and with ambulatory monitoring. Logistic regressions were used to test whether anxiety, neuroticism, extraversion, openness, agreeableness, and conscientiousness predicted the white-coat and masked hypertension phenomena. Age, sex, and antihypertensive medication use were tested as moderators. Results: Significant interactions were found between personality traits and antihypertensive medications in predicting masked and white-coat effects. Only among those taking antihypertensive medication, higher anxiety was associated with a higher risk of pseudo-resistant hypertension due to white-coat effect (odds ratio 1.39, 95% confidence interval 1.01-1.91) and higher conscientiousness was associated with a lower risk of masked uncontrolled hypertension (odds ratio 0.70, 95% confidence interval 0.49-0.99). There were no significant interactions with age or sex. Conclusions: Among those on antihypertensive medications, anxious individuals were more likely to have pseudo-resistant hypertension due to white-coat effect and less conscientious individuals were at increased risk of masked uncontrolled hypertension. Particularly among anxious and less conscientious individuals, ambulatory monitoring may improve the tailoring of pharmacological treatments.
MeSH term(s)	Adult ; Aged ; Antihypertensive Agents/therapeutic use ; Blood Pressure/physiology ; Blood Pressure Determination ; Blood Pressure Monitoring, Ambulatory ; Female ; Humans ; Italy/epidemiology ; Logistic Models ; Male ; Masked Hypertension/epidemiology ; Masked Hypertension/psychology ; Middle Aged ; Odds Ratio ; Personality ; Personality Inventory ; White Coat Hypertension/epidemiology ; White Coat Hypertension/psychology
Chemical Substances	Antihypertensive Agents
Language	English
Publishing date	2014-09-04
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural
ZDB-ID	605532-1
ISSN	1473-5598 ; 0263-6352 ; 0952-1178
ISSN (online)	1473-5598
ISSN	0263-6352 ; 0952-1178
DOI	10.1097/HJH.0000000000000289
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Zs.A 1885: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Serum free thyroxine levels are positively associated with arterial stiffness in the SardiNIA study.

Delitala, Alessandro P / Orrù, Marco / Filigheddu, Fabiana / Pilia, Maria Grazia / Delitala, Giuseppe / Ganau, Antonello / Saba, Pier Sergio / Decandia, Federica / Scuteri, Angelo / Marongiu, Michele / Lakatta, Edward G / Strait, James / Cucca, Francesco

Clinical endocrinology

2014 Volume 82, Issue 4, Page(s) 592–597

Abstract: Objective: Thyroid dysfunction may accelerate atherosclerosis. Aortic pulse wave velocity (PWV) is an early index of arterial stiffness and an important risk factor for cardiovascular disease and might therefore be linked to changes in thyroid activity. ...

Abstract	Objective: Thyroid dysfunction may accelerate atherosclerosis. Aortic pulse wave velocity (PWV) is an early index of arterial stiffness and an important risk factor for cardiovascular disease and might therefore be linked to changes in thyroid activity. We investigated the relationship between thyroid function and carotid-femoral PWV, as an index of arterial stiffness. Design: Cross-sectional cohort study. Patients: Participants from the SardiNIA study. Those being treated for thyroid diseases were excluded, yielding a sample of 5875 aged 14-102. Measurements: Clinical parameters, blood tests including serum TSH and serum FT4, and carotid-femoral PWV were measured. Results: After adjusting for confounders, a direct and linear association between FT4 and PWV was shown (multiple regression analysis). The model containing age, mean blood pressure, body mass index, heart rate, FT4, hypertension, diabetes and dyslipidaemia accounted for 55% of the variation in PWV. Conclusions: Like several other known risk factors, serum FT4 levels are associated with carotid-femoral PWV, suggesting that high FT4 levels have a detrimental effect on aortic stiffness and may contribute to ageing process of the vascular system. This finding may help to understand the pathogenesis of cardiovascular disease and contribute to improve prevention therapy.
MeSH term(s)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; Aorta/pathology ; Atherosclerosis/physiopathology ; Body Mass Index ; Cardiovascular Diseases/physiopathology ; Carotid Arteries/pathology ; Dyslipidemias/blood ; Female ; Femoral Artery/pathology ; Heart Rate ; Humans ; Hyperthyroidism/blood ; Italy ; Male ; Middle Aged ; Pulse Wave Analysis ; Regression Analysis ; Risk Factors ; Thyroid Function Tests ; Thyroid Gland/physiology ; Thyrotropin/blood ; Thyroxine/blood ; Vascular Stiffness
Chemical Substances	Thyrotropin (9002-71-5) ; Thyroxine (Q51BO43MG4)
Language	English
Publishing date	2014-07-14
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Intramural
ZDB-ID	121745-8
ISSN	1365-2265 ; 0300-0664
ISSN (online)	1365-2265
ISSN	0300-0664
DOI	10.1111/cen.12532
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Article ; Online: PRF1

Sidore, Carlo / Orrù, Valeria / Cocco, Eleonora / Steri, Maristella / Inshaw, Jamie Rj / Pitzalis, Maristella / Mulas, Antonella / McGurnaghan, Stuart / Frau, Jessica / Porcu, Eleonora / Busonero, Fabio / Dei, Mariano / Lai, Sandra / Sole, Gabriella / Virdis, Francesca / Serra, Valentina / Poddie, Fausto / Delitala, Alessandro / Marongiu, Michele /

Deidda, Francesca / Pala, Mauro / Floris, Matteo / Masala, Marco / Onengut-Gumuscu, Suna / Robertson, Catherine C / Leoni, Lidia / Frongia, Annapaola / Ricciardi, Maria Rossella / Chessa, Margherita / Olla, Nazario / Lovicu, Mario / Loizedda, Annalisa / Maschio, Andrea / Mereu, Luisa / Ferrigno, Paola / Curreli, Nicolo / Balaci, Lenuta / Loi, Francesco / Ferreli, Liana Ap / Pilia, Maria Grazia / Pani, Antonello / Marrosu, Maria Giovanna / Abecasis, Goncalo R / Rich, Stephen S / Colhoun, Helen / Todd, John A / Schlessinger, David / Fiorillo, Edoardo / Cucca, Francesco / Zoledziewska, Magdalena

Multiple sclerosis (Houndmills, Basingstoke, England)

2020 Volume 27, Issue 9, Page(s) 1332–1340

Abstract: Background: Defective alleles within the : Objective: The aim of this study was to determine the function of hypomorph : Methods: We cross-compare the association data for : Results: We report that : Conclusion: Our results indicate opposing ...

Abstract	Background: Defective alleles within the Objective: The aim of this study was to determine the function of hypomorph Methods: We cross-compare the association data for Results: We report that Conclusion: Our results indicate opposing contributions of the cytotoxic T-cell compartment to MS and T1D pathogenesis.
MeSH term(s)	Autoimmunity/genetics ; Child ; Humans ; Immune System ; Inflammation ; LIM-Homeodomain Proteins ; Muscle Proteins ; Mutation ; Perforin/genetics ; Transcription Factors
Chemical Substances	FHL2 protein, human ; LIM-Homeodomain Proteins ; Muscle Proteins ; PRF1 protein, human ; Transcription Factors ; Perforin (126465-35-8)
Language	English
Publishing date	2020-10-14
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1290669-4
ISSN	1477-0970 ; 1352-4585
ISSN (online)	1477-0970
ISSN	1352-4585
DOI	10.1177/1352458520963937
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Zs.A 4428: Show issues

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Article ; Online: Arterial stiffness and influences of the metabolic syndrome: a cross-countries study.

Scuteri, Angelo / Cunha, Pedro G / Agabiti Rosei, E / Badariere, Jolita / Bekaert, Sofie / Cockcroft, John R / Cotter, Jorge / Cucca, Francesco / De Buyzere, Marc L / De Meyer, Tim / Ferrucci, Luigi / Franco, Osca / Gale, Nichola / Gillebert, Thierry C / Hofman, A / Langlois, Michel / Laucevicius, Aleksandras / Laurent, Stephane / Mattace Raso, Francesco U S /

Atherosclerosis

2014 Volume 233, Issue 2, Page(s) 654–660

Abstract: Specific clusters of metabolic syndrome (MetS) components impact differentially on arterial stiffness, indexed as pulse wave velocity (PWV). Of note, in several population-based studies participating in the MARE (Metabolic syndrome and Arteries REsearch) ...

Abstract	Specific clusters of metabolic syndrome (MetS) components impact differentially on arterial stiffness, indexed as pulse wave velocity (PWV). Of note, in several population-based studies participating in the MARE (Metabolic syndrome and Arteries REsearch) Consortium the occurrence of specific clusters of MetS differed markedly across Europe and the US. The aim of the present study was to investigate whether specific clusters of MetS are consistently associated with stiffer arteries in different populations. We studied 20,570 subjects from 9 cohorts representing 8 different European countries and the US participating in the MARE Consortium. MetS was defined in accordance with NCEP ATPIII criteria as the simultaneous alteration in ≥3 of the 5 components: abdominal obesity (W), high triglycerides (T), low HDL cholesterol (H), elevated blood pressure (B), and elevated fasting glucose (G). PWV measured in each cohort was "normalized" to account for different acquisition methods. MetS had an overall prevalence of 24.2% (4985 subjects). MetS accelerated the age-associated increase in PWV levels at any age, and similarly in men and women. MetS clusters TBW, GBW, and GTBW are consistently associated with significantly stiffer arteries to an extent similar or greater than observed in subjects with alteration in all the five MetS components--even after controlling for age, sex, smoking, cholesterol levels, and diabetes mellitus--in all the MARE cohorts. In conclusion, different component clusters of MetS showed varying associations with arterial stiffness (PWV).
MeSH term(s)	Aged ; Anthropometry ; Comorbidity ; Cross-Sectional Studies ; Diabetes Mellitus/epidemiology ; Dyslipidemias/epidemiology ; Europe/epidemiology ; Female ; Humans ; Hypertension/epidemiology ; Male ; Metabolic Syndrome/blood ; Metabolic Syndrome/epidemiology ; Metabolic Syndrome/pathology ; Middle Aged ; Pulse Wave Analysis ; Sex Factors ; Smoking/epidemiology ; United States/epidemiology ; Vascular Stiffness
Language	English
Publishing date	2014-01-30
Publishing country	Ireland
Document type	Journal Article ; Multicenter Study ; Observational Study ; Research Support, Non-U.S. Gov't
ZDB-ID	80061-2
ISSN	1879-1484 ; 0021-9150
ISSN (online)	1879-1484
ISSN	0021-9150
DOI	10.1016/j.atherosclerosis.2014.01.041
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Article ; Online: Phosphodiesterase 8B gene variants are associated with serum TSH levels and thyroid function.

Arnaud-Lopez, Lisette / Usala, Gianluca / Ceresini, Graziano / Mitchell, Braxton D / Pilia, Maria Grazia / Piras, Maria Grazia / Sestu, Natascia / Maschio, Andrea / Busonero, Fabio / Albai, Giuseppe / Dei, Mariano / Lai, Sandra / Mulas, Antonella / Crisponi, Laura / Tanaka, Toshiko / Bandinelli, Stefania / Guralnik, Jack M / Loi, Angela / Balaci, Lenuta /

Sole, Gabriella / Prinzis, Alessia / Mariotti, Stefano / Shuldiner, Alan R / Cao, Antonio / Schlessinger, David / Uda, Manuela / Abecasis, Gonçalo R / Nagaraja, Ramaiah / Sanna, Serena / Naitza, Silvia

American journal of human genetics

2008 Volume 82, Issue 6, Page(s) 1270–1280

Abstract: Thyroid-stimulating hormone (TSH) controls thyroid growth and hormone secretion through binding to its G protein-coupled receptor (TSHR) and production of cyclic AMP (cAMP). Serum TSH is a sensitive indicator of thyroid function, and overt abnormalities ... ...

Abstract	Thyroid-stimulating hormone (TSH) controls thyroid growth and hormone secretion through binding to its G protein-coupled receptor (TSHR) and production of cyclic AMP (cAMP). Serum TSH is a sensitive indicator of thyroid function, and overt abnormalities in thyroid function lead to common endocrine disorders affecting approximately 10% of individuals over a life span. By genotyping 362,129 SNPs in 4,300 Sardinians, we identified a strong association (p = 1.3 x 10(-11)) between alleles of rs4704397 and circulating TSH levels; each additional copy of the minor A allele was associated with an increase of 0.13 muIU/ml in TSH. The single-nucleotide polymorphism (SNP) is located in intron 1 of PDE8B, encoding a high-affinity cAMP-specific phosphodiesterase. The association was replicated in 4,158 individuals, including additional Sardinians and two genetically distant cohorts from Tuscany and the Old Order Amish (overall p value = 1.9 x 10(-20)). In addition to association of TSH levels with SNPs in PDE8B, our genome scan provided evidence for association with PDE10A and several biologically interesting candidates in a focused analysis of 24 genes. In particular, we found evidence for association of TSH levels with SNPs in the THRB (rs1505287, p = 7.3 x 10(-5)), GNAQ (rs10512065, p = 2.0 x 10(-4)), TG (rs2252696, p = 2.2 x 10(-3)), POU1F1 (rs1976324, p = 3.9 x 10(-3)), PDE4D (rs27178, p = 8.3 x 10(-3)), and TSHR (rs4903957, p = 8.6 x 10(-3)) loci. Overall, the results suggest a primary effect of PDE8B variants on cAMP levels in the thyroid. This would affect production of T4 and T3 and feedback to alter TSH release by the pituitary. PDE8B may thus provide a candidate target for the treatment of thyroid dysfunction.
MeSH term(s)	3',5'-Cyclic-AMP Phosphodiesterases/genetics ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Chromosome Mapping ; Cyclic AMP/metabolism ; Feedback ; Female ; Genetic Variation ; Humans ; Linkage Disequilibrium ; Male ; Middle Aged ; Pituitary Gland/physiology ; Polymorphism, Single Nucleotide ; Thyroid Diseases/enzymology ; Thyroid Diseases/genetics ; Thyroid Diseases/physiopathology ; Thyroid Gland/enzymology ; Thyroid Gland/physiology ; Thyrotropin/blood ; Thyroxine/biosynthesis ; Triiodothyronine/biosynthesis
Chemical Substances	Triiodothyronine (06LU7C9H1V) ; Thyrotropin (9002-71-5) ; Cyclic AMP (E0399OZS9N) ; 3',5'-Cyclic-AMP Phosphodiesterases (EC 3.1.4.17) ; PDE8B protein, human (EC 3.1.4.17) ; Thyroxine (Q51BO43MG4)
Language	English
Publishing date	2008-04-03
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	219384-x
ISSN	1537-6605 ; 0002-9297
ISSN (online)	1537-6605
ISSN	0002-9297
DOI	10.1016/j.ajhg.2008.04.019
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