Genetic regulation of pigment epithelium-derived factor (PEDF): An exome-chip association analysis in Chinese subjects with type 2 diabetes

Chloe Y.Y. Cheung; Chi Ho Lee; Clara S. Tang; Aimin Xu; Ka Wing Au; Carol H.Y. Fong; Kelvin K.K. Ng; Kelvin H.M. Kwok; Wing Sun Chow; Yu Cho Woo; Michele M.A. Yuen; Jo Jo Hai; Kathryn C.B. Tan; Tai Hing Lam; Hung Fat Tse; Pak Chung Sham; Karen S.L. Lam

doi:10.2337/db18-0500

Genetic regulation of pigment epithelium-derived factor (PEDF): An exome-chip association analysis in Chinese subjects with type 2 diabetes

Chloe Y.Y. Cheung, Chi Ho Lee, Clara S. Tang, Aimin Xu, Ka Wing Au, Carol H.Y. Fong, Kelvin K.K. Ng, Kelvin H.M. Kwok, Wing Sun Chow, Yu Cho Woo, Michele M.A. Yuen, Jo Jo Hai, Kathryn C.B. Tan, Tai Hing Lam, Hung Fat Tse, Pak Chung Sham, Karen S.L. Lam

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

17 Citations (Scopus)

Abstract

Elevated circulating levels of pigment epithelium-derived factor (PEDF) have been reported in patients with type 2 diabetes (T2D) and its associated microvascular complications. This study aimed to 1) identify the genetic determinants influencing circulating PEDF levels in a clinical setting of T2D, 2) examine the relationship between circulating PEDF and diabetes complications, and 3) explore the causal relationship between PEDF and diabetes complications. An exome-chip association study on circulating PEDF levels was conducted in 5,385 Chinese subjects with T2D. A meta-analysis of the association results of the discovery stage (n = 2,936) and replication stage (n = 2,449) was performed. The strongest association was detected at SERPINF1 (p.Met72Thr; P_combined = 2.06 3 10²⁵⁷; b [SE] 20.33 [0.02]). Two missense variants of SMYD4 (p.Arg131Ile; P_combined = 7.56 3 10²²⁵; b [SE] 0.21 [0.02]) and SERPINF2 (p.Arg33Trp; P_combined = 8.22 3 10²¹⁰; b [SE] 20.15 [0.02]) showed novel associations at genome-wide significance. Elevated circulating PEDF levels were associated with increased risks of diabetic nephropathy and sight-threatening diabetic retinopathy.

Original language	English
Pages (from-to)	198-206
Number of pages	9
Journal	Diabetes
Volume	68
Issue number	1
DOIs	https://doi.org/10.2337/db18-0500
Publication status	Published - Jan 1 2019
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2018 by the American Diabetes Association.

ASJC Scopus Subject Areas

Internal Medicine
Endocrinology, Diabetes and Metabolism

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10.2337/db18-0500

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Cheung, C. Y. Y., Lee, C. H., Tang, C. S., Xu, A., Au, K. W., Fong, C. H. Y., Ng, K. K. K., Kwok, K. H. M., Chow, W. S., Woo, Y. C., Yuen, M. M. A., Hai, J. J., Tan, K. C. B., Lam, T. H., Tse, H. F., Sham, P. C., & Lam, K. S. L. (2019). Genetic regulation of pigment epithelium-derived factor (PEDF): An exome-chip association analysis in Chinese subjects with type 2 diabetes. Diabetes, 68(1), 198-206. https://doi.org/10.2337/db18-0500

Cheung, CYY, Lee, CH, Tang, CS, Xu, A, Au, KW, Fong, CHY, Ng, KKK, Kwok, KHM, Chow, WS, Woo, YC, Yuen, MMA, Hai, JJ, Tan, KCB, Lam, TH, Tse, HF, Sham, PC & Lam, KSL 2019, 'Genetic regulation of pigment epithelium-derived factor (PEDF): An exome-chip association analysis in Chinese subjects with type 2 diabetes', Diabetes, vol. 68, no. 1, pp. 198-206. https://doi.org/10.2337/db18-0500

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title = "Genetic regulation of pigment epithelium-derived factor (PEDF): An exome-chip association analysis in Chinese subjects with type 2 diabetes",

abstract = "Elevated circulating levels of pigment epithelium-derived factor (PEDF) have been reported in patients with type 2 diabetes (T2D) and its associated microvascular complications. This study aimed to 1) identify the genetic determinants influencing circulating PEDF levels in a clinical setting of T2D, 2) examine the relationship between circulating PEDF and diabetes complications, and 3) explore the causal relationship between PEDF and diabetes complications. An exome-chip association study on circulating PEDF levels was conducted in 5,385 Chinese subjects with T2D. A meta-analysis of the association results of the discovery stage (n = 2,936) and replication stage (n = 2,449) was performed. The strongest association was detected at SERPINF1 (p.Met72Thr; Pcombined = 2.06 3 10257; b [SE] 20.33 [0.02]). Two missense variants of SMYD4 (p.Arg131Ile; Pcombined = 7.56 3 10225; b [SE] 0.21 [0.02]) and SERPINF2 (p.Arg33Trp; Pcombined = 8.22 3 10210; b [SE] 20.15 [0.02]) showed novel associations at genome-wide significance. Elevated circulating PEDF levels were associated with increased risks of diabetic nephropathy and sight-threatening diabetic retinopathy.",

author = "Cheung, {Chloe Y.Y.} and Lee, {Chi Ho} and Tang, {Clara S.} and Aimin Xu and Au, {Ka Wing} and Fong, {Carol H.Y.} and Ng, {Kelvin K.K.} and Kwok, {Kelvin H.M.} and Chow, {Wing Sun} and Woo, {Yu Cho} and Yuen, {Michele M.A.} and Hai, {Jo Jo} and Tan, {Kathryn C.B.} and Lam, {Tai Hing} and Tse, {Hung Fat} and Sham, {Pak Chung} and Lam, {Karen S.L.}",

note = "Publisher Copyright: {\textcopyright} 2018 by the American Diabetes Association.",

year = "2019",

month = jan,

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doi = "10.2337/db18-0500",

language = "English",

volume = "68",

pages = "198--206",

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AU - Cheung, Chloe Y.Y.

AU - Lee, Chi Ho

AU - Tang, Clara S.

AU - Xu, Aimin

AU - Au, Ka Wing

AU - Fong, Carol H.Y.

AU - Ng, Kelvin K.K.

AU - Kwok, Kelvin H.M.

AU - Chow, Wing Sun

AU - Woo, Yu Cho

AU - Yuen, Michele M.A.

AU - Hai, Jo Jo

AU - Tan, Kathryn C.B.

AU - Lam, Tai Hing

AU - Tse, Hung Fat

AU - Sham, Pak Chung

AU - Lam, Karen S.L.

PY - 2019/1/1

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N2 - Elevated circulating levels of pigment epithelium-derived factor (PEDF) have been reported in patients with type 2 diabetes (T2D) and its associated microvascular complications. This study aimed to 1) identify the genetic determinants influencing circulating PEDF levels in a clinical setting of T2D, 2) examine the relationship between circulating PEDF and diabetes complications, and 3) explore the causal relationship between PEDF and diabetes complications. An exome-chip association study on circulating PEDF levels was conducted in 5,385 Chinese subjects with T2D. A meta-analysis of the association results of the discovery stage (n = 2,936) and replication stage (n = 2,449) was performed. The strongest association was detected at SERPINF1 (p.Met72Thr; Pcombined = 2.06 3 10257; b [SE] 20.33 [0.02]). Two missense variants of SMYD4 (p.Arg131Ile; Pcombined = 7.56 3 10225; b [SE] 0.21 [0.02]) and SERPINF2 (p.Arg33Trp; Pcombined = 8.22 3 10210; b [SE] 20.15 [0.02]) showed novel associations at genome-wide significance. Elevated circulating PEDF levels were associated with increased risks of diabetic nephropathy and sight-threatening diabetic retinopathy.

AB - Elevated circulating levels of pigment epithelium-derived factor (PEDF) have been reported in patients with type 2 diabetes (T2D) and its associated microvascular complications. This study aimed to 1) identify the genetic determinants influencing circulating PEDF levels in a clinical setting of T2D, 2) examine the relationship between circulating PEDF and diabetes complications, and 3) explore the causal relationship between PEDF and diabetes complications. An exome-chip association study on circulating PEDF levels was conducted in 5,385 Chinese subjects with T2D. A meta-analysis of the association results of the discovery stage (n = 2,936) and replication stage (n = 2,449) was performed. The strongest association was detected at SERPINF1 (p.Met72Thr; Pcombined = 2.06 3 10257; b [SE] 20.33 [0.02]). Two missense variants of SMYD4 (p.Arg131Ile; Pcombined = 7.56 3 10225; b [SE] 0.21 [0.02]) and SERPINF2 (p.Arg33Trp; Pcombined = 8.22 3 10210; b [SE] 20.15 [0.02]) showed novel associations at genome-wide significance. Elevated circulating PEDF levels were associated with increased risks of diabetic nephropathy and sight-threatening diabetic retinopathy.

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ER -

Genetic regulation of pigment epithelium-derived factor (PEDF): An exome-chip association analysis in Chinese subjects with type 2 diabetes

Abstract

Bibliographical note

ASJC Scopus Subject Areas

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