File Download
  Links for fulltext
     (May Require Subscription)

Article: Genetic regulation of Pigment Epithelium-Derived Factor (PEDF): An exome-chip association analysis in Chinese subjects with Type 2 Diabetes

TitleGenetic regulation of Pigment Epithelium-Derived Factor (PEDF): An exome-chip association analysis in Chinese subjects with Type 2 Diabetes
Authors
Issue Date2019
PublisherAmerican Diabetes Association. The Journal's web site is located at http://diabetes.diabetesjournals.org/
Citation
Diabetes, 2019, v. 68 n. 1, p. 198-206 How to Cite?
AbstractElevated 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 × 10−57; β [SE] −0.33 [0.02]). Two missense variants of SMYD4 (p.Arg131Ile; Pcombined = 7.56 × 10−25; β [SE] 0.21 [0.02]) and SERPINF2 (p.Arg33Trp; Pcombined = 8.22 × 10−10; β [SE] −0.15 [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. Mendelian randomization analysis showed suggestive evidence of a protective role of PEDF on sight-threatening diabetic retinopathy (P = 0.085). Our study provided new insights into the genetic regulation of PEDF and further support for its potential application as a biomarker for diabetic nephropathy and sight-threatening diabetic retinopathy. Further studies to explore the causal relationship of PEDF with diabetes complications are warranted.
Persistent Identifierhttp://hdl.handle.net/10722/272090
ISSN
2020 Impact Factor: 9.461
2020 SCImago Journal Rankings: 3.219
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorCheung, CYY-
dc.contributor.authorLee, CH-
dc.contributor.authorTang, CS-
dc.contributor.authorXu, A-
dc.contributor.authorAu, KW-
dc.contributor.authorFong, CHY-
dc.contributor.authorNg, KKK-
dc.contributor.authorKwok, KHM-
dc.contributor.authorChow, WS-
dc.contributor.authorWoo, YC-
dc.contributor.authorYuen, MMA-
dc.contributor.authorHai, J-
dc.contributor.authorTan, KCB-
dc.contributor.authorLam, TH-
dc.contributor.authorTse, HF-
dc.contributor.authorSham, PC-
dc.contributor.authorLam, KSL-
dc.date.accessioned2019-07-20T10:35:29Z-
dc.date.available2019-07-20T10:35:29Z-
dc.date.issued2019-
dc.identifier.citationDiabetes, 2019, v. 68 n. 1, p. 198-206-
dc.identifier.issn0012-1797-
dc.identifier.urihttp://hdl.handle.net/10722/272090-
dc.description.abstractElevated 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 × 10−57; β [SE] −0.33 [0.02]). Two missense variants of SMYD4 (p.Arg131Ile; Pcombined = 7.56 × 10−25; β [SE] 0.21 [0.02]) and SERPINF2 (p.Arg33Trp; Pcombined = 8.22 × 10−10; β [SE] −0.15 [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. Mendelian randomization analysis showed suggestive evidence of a protective role of PEDF on sight-threatening diabetic retinopathy (P = 0.085). Our study provided new insights into the genetic regulation of PEDF and further support for its potential application as a biomarker for diabetic nephropathy and sight-threatening diabetic retinopathy. Further studies to explore the causal relationship of PEDF with diabetes complications are warranted.-
dc.languageeng-
dc.publisherAmerican Diabetes Association. The Journal's web site is located at http://diabetes.diabetesjournals.org/-
dc.relation.ispartofDiabetes-
dc.titleGenetic regulation of Pigment Epithelium-Derived Factor (PEDF): An exome-chip association analysis in Chinese subjects with Type 2 Diabetes-
dc.typeArticle-
dc.identifier.emailCheung, CYY: cyy0219@hku.hk-
dc.identifier.emailLee, CH: pchlee@hku.hk-
dc.identifier.emailTang, CS: claratang@hku.hk-
dc.identifier.emailXu, A: amxu@hkucc.hku.hk-
dc.identifier.emailAu, KW: aukawing@hku.hk-
dc.identifier.emailFong, CHY: kalofong@hku.hk-
dc.identifier.emailChow, WS: chowws01@hkucc.hku.hk-
dc.identifier.emailWoo, YC: wooyucho@hku.hk-
dc.identifier.emailYuen, MMA: mmayuen@hku.hk-
dc.identifier.emailHai, J: haishjj@hku.hk-
dc.identifier.emailTan, KCB: kcbtan@hkucc.hku.hk-
dc.identifier.emailLam, TH: hrmrlth@hkucc.hku.hk-
dc.identifier.emailTse, HF: hftse@hkucc.hku.hk-
dc.identifier.emailSham, PC: pcsham@hku.hk-
dc.identifier.emailLam, KSL: ksllam@hku.hk-
dc.identifier.authorityCheung, CYY=rp02243-
dc.identifier.authorityLee, CH=rp02043-
dc.identifier.authorityTang, CS=rp02105-
dc.identifier.authorityXu, A=rp00485-
dc.identifier.authorityHai, J=rp02047-
dc.identifier.authorityTan, KCB=rp00402-
dc.identifier.authorityLam, TH=rp00326-
dc.identifier.authorityTse, HF=rp00428-
dc.identifier.authoritySham, PC=rp00459-
dc.identifier.authorityLam, KSL=rp00343-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.2337/db18-0500-
dc.identifier.pmid30305369-
dc.identifier.scopuseid_2-s2.0-85058892762-
dc.identifier.hkuros299567-
dc.identifier.volume68-
dc.identifier.issue1-
dc.identifier.spage198-
dc.identifier.epage206-
dc.identifier.isiWOS:000453906300019-
dc.publisher.placeUnited States-
dc.identifier.issnl0012-1797-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats