GRB14/COBLL1 locus has been shown to be associated with body fat distribution (FD), but
neither the causal gene nor its role in metabolic diseases has been elucidated. We hypothesize that
GRB14/COBLL1 may act as the causal genes for FD-related SNPs (rs10195252 and rs6738627), and that
they may be regulated by SNP to effect obesity-related metabolic traits. We genotyped rs10195252 and
rs6738627 in 2860 subjects with metabolic phenotypes. In a subgroup of 560 subjects, we analyzed
GRB14/COBLL1 gene expression in paired visceral and subcutaneous adipose tissue (AT) samples.
Mediation analyses were used to determine the causal relationship between SNPs, AT GRB14/COBLL1
mRNA expression, and obesity-related traits. In vitro gene knockdown of Grb14/Cobll1 was used to
test their role in adipogenesis. Both gene expressions in AT are correlated with waist circumference.
Visceral GRB14 mRNA expression is associated with FPG and HbA1c. Both SNPs are associated
with triglycerides, FPG, and leptin levels. Rs10195252 is associated with HbA1c and seems to be
mediated by visceral AT GRB14 mRNA expression. Our data support the role of the GRB14/COBLL1
gene expression in body FD and its locus in metabolic sequelae: in particular, lipid metabolism and
glucose homeostasis, which is likely mediated by AT GRB14 transcript levels.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:89882 |
| Date | 16 February 2024 |
| Creators | Sun, Chang, Förster, Franz, Gutsmann, Beate, Moulla, Yusef, Stroh, Christine, Dietrich, Arne, Schön, Michael R., Gärtner, Daniel, Lohmann, Tobias, Dressler, Miriam, Stumvoll, Michael, Blüher, Matthias, Kovacs, Peter, Breitfeld, Jana, Guiu-Jurado, Esther |
| Publisher | MDPI |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 8558, 10.3390/ijms23158558 |
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