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

doi:10.1111/jdi.12805

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

Institute of Public Health

Research output: Contribution to journal › Article › peer-review

12 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 language	English
Pages (from-to)	1067-1074
Number of pages	8
Journal	Journal of Diabetes Investigation
Volume	9
Issue number	5
DOIs	https://doi.org/10.1111/jdi.12805
State	Published - Sep 2018

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1111/jdi.12805

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Chang, Y. C., Hee, S. W., Lee, W. J., Li, H. Y., Chang, T. J., Lin, M. W., Hung, Y. J., Lee, I. T., Hung, K. Y., Assimes, T., Knowles, J. W., Nong, J. Y., Lee, P. C., Chiu, Y. F., & Chuang, L. M. (2018). Genome-wide scan for circulating vascular adhesion protein-1 levels: MACROD2 as a potential transcriptional regulator of adipogenesis. Journal of Diabetes Investigation, 9(5), 1067-1074. https://doi.org/10.1111/jdi.12805

@article{805fb59d1e0844bdb143bbf93f4c828a,

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

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.",

keywords = "Linkage analysis, MACRO domain containing 2 gene, Vascular adhesion protein-1",

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

note = "Publisher Copyright: {\textcopyright} 2018 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd",

year = "2018",

month = sep,

doi = "10.1111/jdi.12805",

language = "English",

volume = "9",

pages = "1067--1074",

journal = "Journal of Diabetes Investigation",

issn = "2040-1116",

publisher = "John Wiley and Sons Inc.",

number = "5",

}

Chang, YC, Hee, SW, Lee, WJ, Li, HY, Chang, TJ, Lin, MW, Hung, YJ, Lee, IT, Hung, KY, Assimes, T, Knowles, JW, Nong, JY, Lee, PC, Chiu, YF & Chuang, LM 2018, 'Genome-wide scan for circulating vascular adhesion protein-1 levels: MACROD2 as a potential transcriptional regulator of adipogenesis', Journal of Diabetes Investigation, vol. 9, no. 5, pp. 1067-1074. https://doi.org/10.1111/jdi.12805

TY - JOUR

T1 - Genome-wide scan for circulating vascular adhesion protein-1 levels

T2 - MACROD2 as a potential transcriptional regulator of adipogenesis

AU - Chang, Yi Cheng

AU - Hee, Siow Wey

AU - Lee, Wei Jei

AU - Li, Hung Yuan

AU - Chang, Tien Jyun

AU - Lin, Ming Wei

AU - Hung, Yi Jen

AU - Lee, I. Te

AU - Hung, Kuan Yi

AU - Assimes, Themistocles

AU - Knowles, Joshua W.

AU - Nong, Jiun Yi

AU - Lee, Po Chu

AU - Chiu, Yen Feng

AU - Chuang, Lee Ming

PY - 2018/9

Y1 - 2018/9

N2 - 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.

AB - 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.

KW - Linkage analysis

KW - MACRO domain containing 2 gene

KW - Vascular adhesion protein-1

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U2 - 10.1111/jdi.12805

DO - 10.1111/jdi.12805

M3 - Article

C2 - 29364582

AN - SCOPUS:85042529887

SN - 2040-1116

VL - 9

SP - 1067

EP - 1074

JO - Journal of Diabetes Investigation

JF - Journal of Diabetes Investigation

IS - 5

ER -

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

Abstract

Keywords

UN SDGs

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