دورية أكاديمية
أعرض في EDS

Rare functional variants in the CRP and G6PC genes modify the relationship between obesity and serum C-reactive protein in white British population.

التفاصيل البيبلوغرافية
العنوان: Rare functional variants in the CRP and G6PC genes modify the relationship between obesity and serum C-reactive protein in white British population.
المؤلفون: Li X; School of Public Health and Emergency Management, Southern University of Science and Technology, Shenzhen, China.; Shenzhen Key Laboratory of Cardiovascular Health and Precision Medicine, Southern University of Science and Technology, Shenzhen, China.; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden., Ploner A; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden., Wang Y; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden., Mak JKL; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden., Lu Y; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden., Magnusson PKE; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden., Jylhävä J; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.; Social Sciences (Health Sciences) and Gerontology Research Center (GEREC), University of Tampere, Tampere, Finland., Hägg S; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
المصدر: Molecular genetics & genomic medicine [Mol Genet Genomic Med] 2023 Dec; Vol. 11 (12), pp. e2255. Date of Electronic Publication: 2023 Jul 26.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: John Wiley & Sons Country of Publication: United States NLM ID: 101603758 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2324-9269 (Electronic) Linking ISSN: 23249269 NLM ISO Abbreviation: Mol Genet Genomic Med Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [Hoboken, NJ] : John Wiley & Sons, [2013]-
مواضيع طبية MeSH: C-Reactive Protein*/genetics , C-Reactive Protein*/analysis , Obesity*/genetics , Polymorphism, Single Nucleotide* , Glucose-6-Phosphatase*/genetics, Humans ; Gene Frequency ; White People/genetics
مستخلص: Background: C-reactive protein (CRP) is a sensitive biomarker of inflammation with moderate heritability. The role of rare functional genetic variants in relation to serum CRP is understudied. We aimed to examine gene mutation burden of protein-altering (PA) and loss-of-function (LOF) variants in association with serum CRP, and to further explore the clinical relevance.
Methods: We included 161,430 unrelated participants of European ancestry from the UK Biobank. Of the rare (minor allele frequency <0.1%) and functional variants, 1,776,249 PA and 266,226 LOF variants were identified. Gene-based burden tests, linear regressions, and logistic regressions were performed to identify the candidate mutations at the gene and variant levels, to estimate the potential interaction effect between the identified PA mutation and obesity, and to evaluate the relative risk of 16 CRP-associated diseases.
Results: At the gene level, PA mutation burdens of the CRP (β = -0.685, p = 2.87e-28) and G6PC genes (β = 0.203, p = 1.50e-06) were associated with reduced and increased serum CRP concentration, respectively. At the variant level, seven PA alleles in the CRP gene decreased serum CRP, of which the per-allele effects were approximately three to seven times greater than that of a common variant in the same locus. The effects of obesity and central obesity on serum CRP concentration were smaller among the PA mutation carriers in the CRP (p interaction  = 0.008) and G6PC gene (p interaction  = 0.034) compared to the corresponding non-carriers.
Conclusion: PA mutation burdens in the CRP and G6PC genes are strongly associated with decreased serum CRP concentrations. As serum CRP and obesity are important predictors of cardiovascular risks in clinics, our observations suggest taking rare genetic factors into consideration might improve the delivery of precision medicine.
(© 2023 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)
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معلومات مُعتمدة: King Gustaf V and Queen Victoria's Foundation of Freemasons; The Foundation for Geriatric Diseases; The Loo & Hans Osterman Foundation; The Magnus Bergwall Foundation; The Strategic Research Program in Epidemiology at Karolinska Institutet; The Swedish National Graduate School for Competitive Science on Ageing and Health; 2018-05973 Swedish Research Council; 2017-00641 Swedish Research Council; 2018-02077 Swedish Research Council; 2015-03255 Swedish Research Council; 2013-2292 FORTE
فهرسة مساهمة: Keywords: C-reactive protein; UK Biobank; loss-of-function variants; obesity; protein-altering variants; rare genetic variants
المشرفين على المادة: 9007-41-4 (C-Reactive Protein)
EC 3.1.3.9 (Glucose-6-Phosphatase)
تواريخ الأحداث: Date Created: 20230726 Date Completed: 20231221 Latest Revision: 20231221
رمز التحديث: 20231221
مُعرف محوري في PubMed: PMC10724514
DOI: 10.1002/mgg3.2255
PMID: 37493001
قاعدة البيانات: MEDLINE
الوصف
تدمد:2324-9269
DOI:10.1002/mgg3.2255