Heritability and circulating concentrations of pregnancy-associated plasma protein-A and stanniocalcin-2 in elderly monozygotic and dizygotic twins
IntroductionPregnancy-associated plasma protein-A (PAPP-A) is an IGF-activating enzyme suggested to influence aging-related diseases. However, knowledge on serum PAPP-A concentration and regulation in elderly subjects is limited. Therefore, we measured serum PAPP-A in elderly same-sex monozygotic (M...
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2023.1193742/full |
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| author | Rikke Hjortebjerg Rikke Hjortebjerg Rikke Hjortebjerg Dorthe Almind Pedersen Jonas Mengel-From Jonas Mengel-From Louise Helskov Jørgensen Kaare Christensen Kaare Christensen Jan Frystyk Jan Frystyk |
| author_facet | Rikke Hjortebjerg Rikke Hjortebjerg Rikke Hjortebjerg Dorthe Almind Pedersen Jonas Mengel-From Jonas Mengel-From Louise Helskov Jørgensen Kaare Christensen Kaare Christensen Jan Frystyk Jan Frystyk |
| author_sort | Rikke Hjortebjerg |
| collection | DOAJ |
| description | IntroductionPregnancy-associated plasma protein-A (PAPP-A) is an IGF-activating enzyme suggested to influence aging-related diseases. However, knowledge on serum PAPP-A concentration and regulation in elderly subjects is limited. Therefore, we measured serum PAPP-A in elderly same-sex monozygotic (MZ) and dizygotic (DZ) twins, as this allowed us to describe the age-relationship of PAPP-A, and to test the hypothesis that serum PAPP-A concentrations are genetically determined. As PAPP-A is functionally related to stanniocalcin-2 (STC2), an endogenous PAPP-A inhibitor, we included measurements on STC2 as well as IGF-I and IGF-II.MethodsThe twin cohort contained 596 subjects (250 MZ twins, 346 DZ twins), whereof 33% were males. The age ranged from 73.2 to 94.3 (mean 78.8) years. Serum was analyzed for PAPP-A, STC2, IGF-I, and IGF-II by commercial immunoassays.ResultsIn the twin cohort, PAPP-A increased with age (r=0.19; P<0.05), whereas IGF-I decreased (r=-0.12; P<0.05). Neither STC2 nor IGF-II showed any age relationship. When analyzed according to sex, PAPP-A correlated positively with age in males (r=0.18; P<0.05) and females (r=0.25; P<0.01), whereas IGF-I correlated inversely in females only (r=-0.15; P<0.01). Males had higher levels of PAPP-A (29%), STC2 (18%) and IGF-I (19%), whereas serum IGF-II was 28% higher in females (all P<0.001). For all four proteins, within-pair correlations were significantly higher for MZ twins than for DZ twins, and they demonstrated substantial and significant heritability, which after adjustment for age and sex averaged 59% for PAPP-A, 66% for STC2, 58% for IGF-I, and 52% for IGF-II.DiscussionThis twin study confirms our hypothesis that the heritability of PAPP-A serum concentrations is substantial, and the same is true for STC2. As regards the age relationship, PAPP-A increases with age, whereas STC2 remains unchanged, thereby supporting the idea that the ability of STC2 to inhibit PAPP-A enzymatic activity decreases with increasing age. |
| first_indexed | 2024-03-13T07:54:47Z |
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| id | doaj.art-1dfdff4a59d94b45932342bdfa855c59 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-03-13T07:54:47Z |
| publishDate | 2023-06-01 |
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| series | Frontiers in Endocrinology |
| spelling | doaj.art-1dfdff4a59d94b45932342bdfa855c592023-06-02T06:01:01ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-06-011410.3389/fendo.2023.11937421193742Heritability and circulating concentrations of pregnancy-associated plasma protein-A and stanniocalcin-2 in elderly monozygotic and dizygotic twinsRikke Hjortebjerg0Rikke Hjortebjerg1Rikke Hjortebjerg2Dorthe Almind Pedersen3Jonas Mengel-From4Jonas Mengel-From5Louise Helskov Jørgensen6Kaare Christensen7Kaare Christensen8Jan Frystyk9Jan Frystyk10Endocrine Research Unit, Department of Endocrinology, Odense University Hospital, Odense, DenmarkDepartment of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, DenmarkSteno Diabetes Center Odense, Odense University Hospital, Odense, DenmarkThe Danish Twin Registry and Danish Aging Research Center, University of Southern Denmark, Odense, DenmarkThe Danish Twin Registry and Danish Aging Research Center, University of Southern Denmark, Odense, DenmarkDepartment of Clinical Genetics, Odense University Hospital, Odense, DenmarkDepartment of Biochemistry, Odense University Hospital, Odense, DenmarkThe Danish Twin Registry and Danish Aging Research Center, University of Southern Denmark, Odense, DenmarkDepartment of Clinical Genetics, Odense University Hospital, Odense, DenmarkEndocrine Research Unit, Department of Endocrinology, Odense University Hospital, Odense, DenmarkDepartment of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, DenmarkIntroductionPregnancy-associated plasma protein-A (PAPP-A) is an IGF-activating enzyme suggested to influence aging-related diseases. However, knowledge on serum PAPP-A concentration and regulation in elderly subjects is limited. Therefore, we measured serum PAPP-A in elderly same-sex monozygotic (MZ) and dizygotic (DZ) twins, as this allowed us to describe the age-relationship of PAPP-A, and to test the hypothesis that serum PAPP-A concentrations are genetically determined. As PAPP-A is functionally related to stanniocalcin-2 (STC2), an endogenous PAPP-A inhibitor, we included measurements on STC2 as well as IGF-I and IGF-II.MethodsThe twin cohort contained 596 subjects (250 MZ twins, 346 DZ twins), whereof 33% were males. The age ranged from 73.2 to 94.3 (mean 78.8) years. Serum was analyzed for PAPP-A, STC2, IGF-I, and IGF-II by commercial immunoassays.ResultsIn the twin cohort, PAPP-A increased with age (r=0.19; P<0.05), whereas IGF-I decreased (r=-0.12; P<0.05). Neither STC2 nor IGF-II showed any age relationship. When analyzed according to sex, PAPP-A correlated positively with age in males (r=0.18; P<0.05) and females (r=0.25; P<0.01), whereas IGF-I correlated inversely in females only (r=-0.15; P<0.01). Males had higher levels of PAPP-A (29%), STC2 (18%) and IGF-I (19%), whereas serum IGF-II was 28% higher in females (all P<0.001). For all four proteins, within-pair correlations were significantly higher for MZ twins than for DZ twins, and they demonstrated substantial and significant heritability, which after adjustment for age and sex averaged 59% for PAPP-A, 66% for STC2, 58% for IGF-I, and 52% for IGF-II.DiscussionThis twin study confirms our hypothesis that the heritability of PAPP-A serum concentrations is substantial, and the same is true for STC2. As regards the age relationship, PAPP-A increases with age, whereas STC2 remains unchanged, thereby supporting the idea that the ability of STC2 to inhibit PAPP-A enzymatic activity decreases with increasing age.https://www.frontiersin.org/articles/10.3389/fendo.2023.1193742/fullagingIGF-IIGF-IIPAPP-ASTC2twin |
| spellingShingle | Rikke Hjortebjerg Rikke Hjortebjerg Rikke Hjortebjerg Dorthe Almind Pedersen Jonas Mengel-From Jonas Mengel-From Louise Helskov Jørgensen Kaare Christensen Kaare Christensen Jan Frystyk Jan Frystyk Heritability and circulating concentrations of pregnancy-associated plasma protein-A and stanniocalcin-2 in elderly monozygotic and dizygotic twins Frontiers in Endocrinology aging IGF-I IGF-II PAPP-A STC2 twin |
| title | Heritability and circulating concentrations of pregnancy-associated plasma protein-A and stanniocalcin-2 in elderly monozygotic and dizygotic twins |
| title_full | Heritability and circulating concentrations of pregnancy-associated plasma protein-A and stanniocalcin-2 in elderly monozygotic and dizygotic twins |
| title_fullStr | Heritability and circulating concentrations of pregnancy-associated plasma protein-A and stanniocalcin-2 in elderly monozygotic and dizygotic twins |
| title_full_unstemmed | Heritability and circulating concentrations of pregnancy-associated plasma protein-A and stanniocalcin-2 in elderly monozygotic and dizygotic twins |
| title_short | Heritability and circulating concentrations of pregnancy-associated plasma protein-A and stanniocalcin-2 in elderly monozygotic and dizygotic twins |
| title_sort | heritability and circulating concentrations of pregnancy associated plasma protein a and stanniocalcin 2 in elderly monozygotic and dizygotic twins |
| topic | aging IGF-I IGF-II PAPP-A STC2 twin |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2023.1193742/full |
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