Genome-wide scan for circulating vascular adhesion protein-1 levels: MACROD2 as a potential transcriptional regulator of adipogenesis

Yi Cheng Chang, Siow Wey Hee, Wei Jei Lee, Hung Yuan Li, Tien Jyun Chang, Ming Wei Lin, Yi Jen Hung, I. Te Lee, Kuan Yi Hung, Themistocles Assimes, Joshua W. Knowles, Jiun Yi Nong, Po Chu Lee, Yen Feng Chiu*, Lee Ming Chuang

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Aims/Introduction: Vascular adhesion protein-1 (VAP-1) is a membrane-bound amine oxidase highly expressed in mature adipocytes and released into the circulation. VAP-1 has been strongly implicated in several pathological processes, including diabetes, inflammation, hypertension, hepatic steatosis and renal diseases, and is an important disease marker and therapeutic target. Here, we aimed to identify the genetic loci for circulating VAP-1 levels. Materials and Methods: We carried out a genomic-wide linkage scan for the quantitative trait locus of circulating VAP-1 levels in 1,100 Han Chinese individuals from 398 families in the Stanford Asian Pacific Program for Hypertension and Insulin Resistance study. Regional association fine mapping was carried out using additional single-nucleotide polymorphisms. Results: The estimated heritability of circulating VAP-1 levels is high (h2 = 69%). The most significant quantitative trait locus for circulating VAP-1 was located at 38 cM on chromosome 20, with a maximum empirical logarithm of odds score of 4.11 (P = 6.86 × 10−6) in females. Regional single-nucleotide polymorphism fine mapping within a 1-unit support region showed the strongest association signals in the MACRO domain containing 2 (MACROD2) gene in females (P = 5.38 × 10−6). Knockdown of MACROD2 significantly suppressed VAP-1 expression in human adipocytes, as well as the expression of key adipogenic genes. Furthermore, MACROD2 expression was found to be positively associated with VAP-1 in human visceral adipose tissue. Conclusion: MACROD2 is a potential genetic determinant of serum VAP-1 levels, probably through transcriptional regulation of adipogenesis.

Original languageEnglish
Pages (from-to)1067-1074
Number of pages8
JournalJournal of Diabetes Investigation
Volume9
Issue number5
DOIs
StatePublished - Sep 2018

Keywords

  • Linkage analysis
  • MACRO domain containing 2 gene
  • Vascular adhesion protein-1

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