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Serum Vaspin Concentrations Are Closely Related to Insulin Resistance, and rs77060950 at SERPINA12 Genetically Defines Distinct Group with Higher Serum Levels in Japanese Population
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CONTEXT: Vaspin is an adipokine with insulin-sensitizing effects identified from visceral adipose tissues of genetically obese rats. OBJECTIVE: We investigated genetic and nongenetic factors that define serum concentrations of vaspin. DESIGN, SETTING AND PARTICIPANTS: Vaspin levels were measured with RIA in Japanese subjects with normal fasting plasma glucose (NFG; n = 259) and type 2 diabetes patients (T2D; n = 275). Single nucleotide polymorphisms (SNP) at SERPINA12 (vaspin) gene locus were discovered, and five SNP were genotyped in the subjects with varied body mass index (n = 1138). RESULTS: The level of serum vaspin in 93% of the samples was found to vary from 0.2 to nearly 2 ng/ml in NFG subjects (n = 259) and from 0.2 to nearly 3 ng/ml in T2D patients (n = 275) (Vaspin(Low) group), whereas a significant subpopulation (7%) in both groups displayed much higher levels of 10-40 ng/ml (Vaspin(High) group). In the Vaspin(Low) group, serum vaspin levels in T2D were significantly higher than healthy subjects (0.99 ± 0.04 vs. 0.86 ± 0.02 ng/ml; P < 0.01). Both in T2D and genotyped Japanese population, serum vaspin levels closely correlated with homeostasis model of assessment for insulin resistance rather than anthropometric parameters. By genotyping, rs77060950 tightly linked to serum vaspin levels, i.e. CC (0.6 ± 0.4 ng/ml), CA (18.4 ± 9.6 ng/ml), and AA (30.5 ± 5.1 ng/ml) (P < 2 × 10(-16)). Putative GATA-2 and GATA-3 binding consensus site was found at rs77060950. CONCLUSIONS: Serum vaspin levels were related to insulin resistance, and higher levels of serum vaspin in 7% of the Japanese population are closely linked to minor allele sequence (A) of rs77060950.
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At the SERPINA12 locus, a cis primary association was found in all four non-European ancestries, in proxy with the intronic functional variant rs77060950 (r2 = 1), where the minor T allele was associated with higher SERPINA12 (vaspin) levels.
“Notably, at the SERPINA12 locus, we found a cis primary association in all four non-European ancestries, in proxy with the intronic functional variant rs77060950 30 (r 2 = 1) where the minor T allele was associated with higher SERPINA12 (vaspin) levels”
From Plasma proteomic associations with genetics and health in the UK Biobank (2023) · cites this paper as [30]
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cDNA sequence of human apolipoprotein(a) is homologous to plasminogen
McLean, J. W., Tomlinson, J. E., Kuang, W.-J., Eaton, D. L., Chen, E. Y., Fless, G. M., Scanu, A. M., & Lawn, R. M. (1987) · Nature · doi:10.1038/330132a0 · Cited by 1,886
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Plasma proteomic associations with genetics and health in the UK Biobank
Sun, B. B., Chiou, J., Traylor, M., Benner, C., Hsu, Y.-H., Richardson, T. G., Surendran, P., Mahajan, A., Robins, C., Vasquez-Grinnell, S. G., et al. (2023) · Nature · doi:10.1038/s41586-023-06592-6 · Cited by 1,880
Metadata
- Authors
- Teshigawara, S., Wada, J., Hida, K., Nakatsuka, A., Eguchi, J., Murakami, K., Kanzaki, M., Inoue, K., Terami, T., Katayama, A., Iseda, I., Matsushita, Y., Miyatake, N., McDonald, J. F., Hotta, K., & Makino, H.
- Affiliations
- Okayama University (JP)
- Kagawa University (JP)
- Kyoto University (JP)
- Corresponding author
- Wada, Jun
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2012-07
- Volume
- 97
- Issue
- 7
- Pages
- E1202-E1207
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2039908541
- Cited by
- 65
- References
- 1
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 4 · 2022: 1 · 2021: 6 · 2020: 6 · 2019: 6 · 2018: 4 · 2017: 5 · 2016: 3 · 2015: 3 · 2014: 9 · 2013: 7 · 2012: 5
- FWCI
- 5.42
- Type
- journal article
- Language
- en
- Open access
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Okayama University Scientific Achievement Repository (Okayama University) (submittedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Japan Society for the Promotion of Science (24790926, 23390241, 23659470)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Keywords
- vaspin, SERPINA12, insulin resistance, type 2 diabetes, single nucleotide polymorphisms, serum adipokine levels, genetic association, Japanese population, body mass index, HOMA-IR, visceral adipose tissue, obesity, adipokine secretion
- MeSH terms
- Adult, Aged, Blood Glucose, Diabetes Mellitus, Type 2, Fasting, Female, Humans, Insulin Resistance, Male, Middle Aged, Osmolar Concentration, Population, Serpins, Case-Control Studies, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Asian People
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