Dataset Information

Heritability and circulating concentrations of pregnancy-associated plasma protein-A and stanniocalcin-2 in elderly monozygotic and dizygotic twins.

ABSTRACT:

Introduction

Pregnancy-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.

Methods

The 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.

Results

In 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.

Discussion

This 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.

SUBMITTER: Hjortebjerg R

PROVIDER: S-EPMC10272750 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Heritability and circulating concentrations of pregnancy-associated plasma protein-A and stanniocalcin-2 in elderly monozygotic and dizygotic twins.

Hjortebjerg Rikke R Pedersen Dorthe Almind DA Mengel-From Jonas J Jørgensen Louise Helskov LH Christensen Kaare K Frystyk Jan J

Frontiers in endocrinology 20230602

<h4>Introduction</h4>Pregnancy-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 i ...[more]

PMID: 37334305

Similar Datasets

Project description:ImportanceLow birth weight is associated with an increased likelihood of neurodivergence and neurodevelopmental conditions (NDCs) such as autism, attention-deficit/hyperactivity disorder (ADHD), and intellectual disability. However, it is unclear whether birth weight contributes independently to NDCs or whether the association is predominantly driven by genetic predisposition.ObjectiveTo estimate the associations between birth weight and dimensional (trait) and categorical (diagnoses) NDC outcomes, while adjusting for genetic risks.Design, setting, and participantsA co-twin design was applied to this case-control study conducted in Sweden. Diagnostic assessments were conducted between August 2011 and March 2022, within the Roots of Autism and ADHD Twin Study in Sweden (RATSS) during a 2.5-day participant visit to the clinic. The RATSS sample comprised phenotyped monozygotic and dizygotic twins enriched for NDCs. Data analysis was conducted in November 2022.ExposureBirth weight.Main outcomes and measuresCategorical and dimensional operationalizations of autism, ADHD, and intellectual disability were assessed. Generalized estimating equation models were fitted across and within twin pairs.ResultsThe study sample included 393 twins: 230 were monozygotic and 159 were dizygotic (zygosity was unknown for 4). Their median age was 15 (range, 8-37) years. There were 185 female participants (47.1%) and 208 male participants (52.9%). Across twin pairs, higher birth weight was associated with fewer autistic traits (unstandardized β [B], -5.51 [95% CI, -10.09 to -0.94]) and lower odds of autism diagnosis (OR, 0.63 [95% CI, 0.45 to 0.88]) and intellectual disability (OR, 0.42 [95% CI, 0.19 to 0.92]). Within pairs, the association between birth weight and dimensional autism (B, -17.35 [95% CI, -28.66 to -6.04]) and categorical autism (OR, 0.02 [95% CI, 0.001 to 0.42]) remained among monozygotic pairs but not dizygotic pairs. In addition, higher birth weight was associated with lower odds of ADHD diagnosis (OR, 0.003 [95% CI, 0 to 0.70]), fewer ADHD traits (B, -0.25 [95% CI, -0.39 to -0.11]), and higher IQ ratings (B, 7.43 [95% CI, 1.05 to 13.82]) among monozygotic twins.Conclusions and relevanceThe findings of this co-twin study suggest an association between low birth weight and NDCs, but they also acknowledge the importance of genetics because the associations observed were only statically significant among monozygotic twins. It is of pivotal importance to facilitate early identification of factors contributing to fetal growth restriction to minimize detrimental outcomes.

Project description:The early-life microbiota triggers life-long effects on physiological functions and health disorders. Previous studies in adult twins or animal models have revealed associations between host genetics and the harmonious microbiota. However, such associations may be obscured by the fact that each intra-pair of twins will continually encounter various environmental factors as they grow up. Here, we collected the meconium samples from nineteen dizygotic pairs (DZ, n = 38) and nine monozygotic pairs (MZ, n = 18) with cesarean delivery, and 16S rRNA gene sequencing was performed to profile the microbiome at birth. Diversity analysis showed that alpha diversity was not significantly different between two groups, whereas beta diversity of MZ twins was significantly lower than that of either DZ twins or unrelated individuals (i.e., randomly selected individual pairs of non-twinship) (p < 0.05). Two groups had very similar microbial classifications but different relative abundances of certain taxa including more Firmicutes (p = 0.05, Wilcoxon test) at the phylum level and lower abundances of five genera (p < 0.05) in DZ group compared to MZ group, including Rheinheimera, Proteus, SMB53, Sphingobium, and Megamonas. Co-occurrence analysis in each group showed slightly more complicated microbial interactions in DZ than MZ twins, although 22 shared bacterial genera co-existed in two groups, with both Rheinheimera and Megamonas having different centralities in their respective co-occurrence networks. Mean intra-class correlation coefficient (ICC) were also significantly higher for MZ (0.312) compared to DZ twins (0.138) (p < 0.05). The predicted microbial gene functions related to carbohydrate were higher in DZ group, whereas folding, sorting, degradation, cell motility pathways and energy metabolism were markedly over-represented in the microbiota of MZ group. In summary, our study uncovered that microbial diversity and components of the meconium microbiome between DZ and MZ twins were partially consistent with that in singleton neonates by cesarean delivery, but several distinctions related to the heritability supported genetic contributions to intestinal microbiome in early life.

Dataset Information

Heritability and circulating concentrations of pregnancy-associated plasma protein-A and stanniocalcin-2 in elderly monozygotic and dizygotic twins.

Introduction

Methods

Results

Discussion

Publications

Heritability and circulating concentrations of pregnancy-associated plasma protein-A and stanniocalcin-2 in elderly monozygotic and dizygotic twins.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets