Twin Study: Genetic and Epigenetic Factors Affecting Circulating Adiponectin Levels

Hasegawa, Mika; Taniguchi, Jumpei; Ueda, Hiroshi; Watanabe, Mikio

doi:10.1210/clinem/dgac532

Cited by 6 publications

(7 citation statements)

References 42 publications

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“…Gene expression can be modified by epigenetic changes, which do not alter the DNA sequence [ 8 ]. The attachment of methyl groups to cytosine rings within guanine residues, a process called DNA methylation, is the most extensively investigated epigenetic modification due to its relative ease of measurement [ 7 ].…”

Section: Discussionmentioning

confidence: 99%

“…We observed that lower levels of 5mdC/dG were related to higher levels of serum adiponectin. Previous studies have shown that epigenetic modifications can affect genes expression related to adiponectin [ 7 , 8 ]. A Japanese study involving 232 pairs of monozygotic twins conducted an epigenetic variation association study to identify epigenetic regulators influencing adiponectin levels.…”

Section: Discussionmentioning

confidence: 99%

“…It has been shown that aldosterone may downregulate the gene expression of adiponectin [ 6 ]. Additionally, research has revealed that epigenetic modifications, which do not involve changes to the DNA sequence but can affect gene expression, can alter the expression of adiponectin-related genes [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

“…Past research has suggested that DNA methylation, a well-studied form of epigenetic regulation, may be involved in the link between DEHP and health outcomes [ 19 , 20 ]. Although it is known that epigenetic modifications can also affect adiponectin levels [ 7 , 8 ], the potential impact of these changes on the relationship between DEHP and adiponectin has yet to be explored.…”

Section: Introductionmentioning

confidence: 99%

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The role of angiotensin I-converting enzyme gene polymorphism and global DNA methylation in the negative associations between urine di-(2-ethylhexyl) phthalate metabolites and serum adiponectin in a young Taiwanese population

et al. 2023

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Background Adiponectin is a key protein produced in adipose tissue, with crucial involvement in multiple metabolic processes. Di-(2-ethylhexyl) phthalate (DEHP), one of the phthalate compounds used as a plasticizer, has been shown to decrease adiponectin levels in vitro and in vivo studies. However, the role of angiotensin I-converting enzyme (ACE) gene polymorphism and epigenetic changes in the relationship between DEHP exposure and adiponectin levels is not well understood. Methods This study examined the correlation between urine levels of DEHP metabolite, epigenetic marker 5mdC/dG, ACE gene phenotypes, and adiponectin levels in a sample of 699 individuals aged 12–30 from Taiwan. Results Results showed a positive relationship between mono-2-ethylhexyl phthalate (MEHP) and 5mdC/dG, and a negative association between both MEHP and 5mdC/dG with adiponectin. The study found that the inverse relationship between MEHP and adiponectin was stronger when levels of 5mdC/dG were above the median. This was supported by differential unstandardized regression coefficients (− 0.095 vs. − 0.049, P value for interaction = 0.038)). Subgroup analysis also showed a negative correlation between MEHP and adiponectin in individuals with the I/I ACE genotype, but not in those with other genotypes, although the P value for interaction was borderline significant (0.06). The structural equation model analysis indicated that MEHP has a direct inverse effect on adiponectin and an indirect effect via 5mdC/dG. Conclusions In this young Taiwanese population, our findings suggest that urine MEHP levels are negatively correlated with serum adiponectin levels, and epigenetic modifications may play a role in this association. Further study is needed to validate these results and determine causality.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The role of angiotensin I-converting enzyme gene polymorphism and global DNA methylation in the negative associations between urine di-(2-ethylhexyl) phthalate metabolites and serum adiponectin in a young Taiwanese population

et al. 2023

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“…Insufficient consideration of confounding factors that may impact both protein levels and risk of infection in the neonatal period is another reason [7]. The twin design could control for shared genetic and environmental confounding factors and thus may enhance the strength of causal evidence in omics research [8].…”

Section: Introductionmentioning

confidence: 99%

Associations between multiple immune-response-related proteins and neonatal infection: a proximity extension assay based proteomic study in cord plasma of twins

Chen,

Tan,

Zheng

et al. 2024

Preprint

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Background. Given their immature immune system, neonates are highly susceptible to infection, a major cause of neonatal death. However, associations between immune-response-related proteins and risk of neonatal infection have yet been systematically investigated. Methods. We conducted a nested case-control study of 149 twins (60 cases and 89 controls, including 34 pairs of discordant twins), within the Shenzhen Baoan Birth and Twin (SZBBTwin) cohort. Using proximity extension assay of Olink Proteomics, 92 immune-response-related proteins were measured in samples of cord plasma. All twins were followed for a diagnosis of infection from birth until 27 days of age. Wilcoxon rank-sum test was used to determine differentially expressed proteins (DEPs), and multivariable logistic regression was used to assess the associations of the levels of proteins with neonatal infection. The receiver operating characteristic curve was plotted to evaluate the predictive performance of DEPs. Enrichment analysis was performed to annotate potential functions and pathways of DEPs. Results. Five DEPs (ITGA11, FCRL6, DDX58, SH2D1A, and EDAR) were identified for neonatal infection. A higher cord plasma level of integrin alpha 11 (ITGA11) was associated with a higher risk of neonatal infection in both the analyses of all twins and discordant twins. The area under the curve achieved 0.835 for the five DEPs. The identified DEPs were mainly involved in immune function and protein binding, and most of them were enriched in the nuclear factor kappa-B pathway. Conclusion. Multiple immune-response-related proteins in cord plasma, particularly ITGA11, are associated with the risk of neonatal infection.

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Whole genome sequencing of mouse lines divergently selected for fatness (FLI) and leanness (FHI) revealed several genetic variants as candidates for novel obesity genes

Šimon,

Mikec,

Atanur

et al. 2024

Genes Genom

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Background Analysing genomes of animal model organisms is widely used for understanding the genetic basis of complex traits and diseases, such as obesity, for which only a few mouse models exist, however, without their lean counterparts. Objective To analyse genetic differences in the unique mouse models of polygenic obesity (Fat line) and leanness (Lean line) originating from the same base population and established by divergent selection over more than 60 generations. Methods Genetic variability was analysed using WGS. Variants were identified with GATK and annotated with Ensembl VEP. g.Profiler, WebGestalt, and KEGG were used for GO and pathway enrichment analysis. miRNA seed regions were obtained with miRPathDB 2.0, LncRRIsearch was used to predict targets of identified lncRNAs, and genes influencing adipose tissue amount were searched using the IMPC database. Results WGS analysis revealed 6.3 million SNPs, 1.3 million were new. Thousands of potentially impactful SNPs were identified, including within 24 genes related to adipose tissue amount. SNP density was highest in pseudogenes and regulatory RNAs. The Lean line carries SNP rs248726381 in the seed region of mmu-miR-3086-3p, which may affect fatty acid metabolism. KEGG analysis showed deleterious missense variants in immune response and diabetes genes, with food perception pathways being most enriched. Gene prioritisation considering SNP GERP scores, variant consequences, and allele comparison with other mouse lines identified seven novel obesity candidate genes: 4930441H08Rik, Aff3, Fam237b, Gm36633, Pced1a, Tecrl, and Zfp536. Conclusion WGS revealed many genetic differences between the lines that accumulated over the selection period, including variants with potential negative impacts on gene function. Given the increasing availability of mouse strains and genetic polymorphism catalogues, the study is a valuable resource for researchers to study obesity.

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Twin Study: Genetic and Epigenetic Factors Affecting Circulating Adiponectin Levels

Cited by 6 publications

References 42 publications

The role of angiotensin I-converting enzyme gene polymorphism and global DNA methylation in the negative associations between urine di-(2-ethylhexyl) phthalate metabolites and serum adiponectin in a young Taiwanese population

The role of angiotensin I-converting enzyme gene polymorphism and global DNA methylation in the negative associations between urine di-(2-ethylhexyl) phthalate metabolites and serum adiponectin in a young Taiwanese population

Associations between multiple immune-response-related proteins and neonatal infection: a proximity extension assay based proteomic study in cord plasma of twins

Whole genome sequencing of mouse lines divergently selected for fatness (FLI) and leanness (FHI) revealed several genetic variants as candidates for novel obesity genes

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