Skip to main content
Erschienen in: Diabetologia 6/2015

01.06.2015 | Article

Common variants in or near ZNRF1, COLEC12, SCYL1BP1 and API5 are associated with diabetic retinopathy in Chinese patients with type 2 diabetes

verfasst von: Danfeng Peng, Jie Wang, Rong Zhang, Feng Jiang, Shanshan Tang, Miao Chen, Jing Yan, Xue Sun, Shiyun Wang, Tao Wang, Dandan Yan, Yuqian Bao, Cheng Hu, Weiping Jia

Erschienen in: Diabetologia | Ausgabe 6/2015

Einloggen, um Zugang zu erhalten

Abstract

Aims/hypothesis

Three recent genome-wide association studies (GWAS) identified several single-nucleotide polymorphisms (SNPs) with modest effects on diabetic retinopathy in Mexican-American and white patients with diabetes. This study aimed to evaluate the effects of these variants on diabetic retinopathy in Chinese patients with type 2 diabetes.

Methods

A total of 1,972 patients with type 2 diabetes were recruited to this study, including 819 patients with diabetic retinopathy and 1,153 patients with diabetes of ≥5 years duration but without retinopathy. Forty SNPs associated with diabetic retinopathy in three GWAS were genotyped. Fundus photography was performed to diagnose and classify diabetic retinopathy.

Results

rs17684886 in ZNRF1 and rs599019 near COLEC12 were associated with diabetic retinopathy (OR 0.812, p = 0.0039 and OR 0.835, p = 0.0116, respectively) and with the severity of diabetic retinopathy (p = 0.0365 and p = 0.0252, respectively, for trend analysis). Sub-analysis in patients with diabetic retinopathy revealed that rs6427247 near SCYL1BP1 (also known as GORAB) and rs899036 near API5 were associated with severe diabetic retinopathy (OR 1.368, p = 0.0333 and OR 0.340, p = 0.0005, respectively). The associations between rs6427247 and rs899036 and severe diabetic retinopathy became more evident after a meta-analysis of published GWAS data (OR 1.577, p = 2.01 × 10−4 for rs6427247; OR 0.330, p = 5.84 × 10−7 for rs899036).

Conclusions/interpretation

We determined that rs17684886 and rs599019 are associated with diabetic retinopathy and that rs6427247 and rs899036 are associated with severe diabetic retinopathy in Chinese patients with type 2 diabetes.
Literatur
1.
Zurück zum Zitat Klein BE (2007) Overview of epidemiologic studies of diabetic retinopathy. Ophthalmic Epidemiol 14:179–183CrossRefPubMed Klein BE (2007) Overview of epidemiologic studies of diabetic retinopathy. Ophthalmic Epidemiol 14:179–183CrossRefPubMed
3.
Zurück zum Zitat Stratton IM, Adler AI, Neil HA et al (2000) Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 321:405–412CrossRefPubMedCentralPubMed Stratton IM, Adler AI, Neil HA et al (2000) Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 321:405–412CrossRefPubMedCentralPubMed
4.
Zurück zum Zitat Tapp RJ, Shaw JE, Harper CA et al (2003) The prevalence of and factors associated with diabetic retinopathy in the Australian population. Diabetes Care 26:1731–1737CrossRefPubMed Tapp RJ, Shaw JE, Harper CA et al (2003) The prevalence of and factors associated with diabetic retinopathy in the Australian population. Diabetes Care 26:1731–1737CrossRefPubMed
6.
Zurück zum Zitat Sun JK, Keenan HA, Cavallerano JD et al (2011) Protection from retinopathy and other complications in patients with type 1 diabetes of extreme duration: the Joslin 50-Year Medalist Study. Diabetes Care 34:968–974CrossRefPubMedCentralPubMed Sun JK, Keenan HA, Cavallerano JD et al (2011) Protection from retinopathy and other complications in patients with type 1 diabetes of extreme duration: the Joslin 50-Year Medalist Study. Diabetes Care 34:968–974CrossRefPubMedCentralPubMed
8.
9.
Zurück zum Zitat The Diabetes Control and Complications Trial Research Group (1997) Clustering of long-term complications in families with diabetes in the diabetes control and complications trial. Diabetes 46:1829–1839CrossRef The Diabetes Control and Complications Trial Research Group (1997) Clustering of long-term complications in families with diabetes in the diabetes control and complications trial. Diabetes 46:1829–1839CrossRef
10.
Zurück zum Zitat Zhang X, Gao Y, Zhou Z, Wang J, Zhou Q, Li Q (2010) Familial clustering of diabetic retinopathy in Chongqing, China, type 2 diabetic patients. Eur J Ophthalmol 20:911–918PubMed Zhang X, Gao Y, Zhou Z, Wang J, Zhou Q, Li Q (2010) Familial clustering of diabetic retinopathy in Chongqing, China, type 2 diabetic patients. Eur J Ophthalmol 20:911–918PubMed
11.
Zurück zum Zitat Rema M, Saravanan G, Deepa R, Mohan V (2002) Familial clustering of diabetic retinopathy in South Indian type 2 diabetic patients. Diabet Med 19:910–916CrossRefPubMed Rema M, Saravanan G, Deepa R, Mohan V (2002) Familial clustering of diabetic retinopathy in South Indian type 2 diabetic patients. Diabet Med 19:910–916CrossRefPubMed
12.
Zurück zum Zitat Looker HC, Nelson RG, Chew E et al (2007) Genome-wide linkage analyses to identify Loci for diabetic retinopathy. Diabetes 56:1160–1166CrossRefPubMed Looker HC, Nelson RG, Chew E et al (2007) Genome-wide linkage analyses to identify Loci for diabetic retinopathy. Diabetes 56:1160–1166CrossRefPubMed
14.
Zurück zum Zitat Arar NH, Freedman BI, Adler SG et al (2008) Heritability of the severity of diabetic retinopathy: the FIND-Eye study. Invest Ophthalmol Vis Sci 49:3839–3845CrossRefPubMedCentralPubMed Arar NH, Freedman BI, Adler SG et al (2008) Heritability of the severity of diabetic retinopathy: the FIND-Eye study. Invest Ophthalmol Vis Sci 49:3839–3845CrossRefPubMedCentralPubMed
16.
Zurück zum Zitat Fu YP, Hallman DM, Gonzalez VH et al (2010) Identification of diabetic retinopathy genes through a genome-wide association study among Mexican-Americans from Starr County, Texas. J Ophthalmol 2010:861291CrossRefPubMedCentralPubMed Fu YP, Hallman DM, Gonzalez VH et al (2010) Identification of diabetic retinopathy genes through a genome-wide association study among Mexican-Americans from Starr County, Texas. J Ophthalmol 2010:861291CrossRefPubMedCentralPubMed
17.
Zurück zum Zitat Grassi MA, Tikhomirov A, Ramalingam S, Below JE, Cox NJ, Nicolae DL (2011) Genome-wide meta-analysis for severe diabetic retinopathy. Hum Mol Genet 20:2472–2481CrossRefPubMedCentralPubMed Grassi MA, Tikhomirov A, Ramalingam S, Below JE, Cox NJ, Nicolae DL (2011) Genome-wide meta-analysis for severe diabetic retinopathy. Hum Mol Genet 20:2472–2481CrossRefPubMedCentralPubMed
18.
Zurück zum Zitat Grassi MA, Tikhomirov A, Ramalingam S et al (2012) Replication analysis for severe diabetic retinopathy. Invest Ophthalmol Vis Sci 53:2377–2381CrossRefPubMedCentralPubMed Grassi MA, Tikhomirov A, Ramalingam S et al (2012) Replication analysis for severe diabetic retinopathy. Invest Ophthalmol Vis Sci 53:2377–2381CrossRefPubMedCentralPubMed
19.
Zurück zum Zitat Jia W, Gao X, Pang C et al (2009) Prevalence and risk factors of albuminuria and chronic kidney disease in Chinese population with type 2 diabetes and impaired glucose regulation: Shanghai diabetic complications study (SHDCS). Nephrol Dial Transplant 24:3724–3731CrossRefPubMed Jia W, Gao X, Pang C et al (2009) Prevalence and risk factors of albuminuria and chronic kidney disease in Chinese population with type 2 diabetes and impaired glucose regulation: Shanghai diabetic complications study (SHDCS). Nephrol Dial Transplant 24:3724–3731CrossRefPubMed
20.
Zurück zum Zitat Hu C, Zhang R, Wang C et al (2010) Effects of GCK, GCKR, G6PC2 and MTNR1B variants on glucose metabolism and insulin secretion. PLoS One 5:e11761CrossRefPubMedCentralPubMed Hu C, Zhang R, Wang C et al (2010) Effects of GCK, GCKR, G6PC2 and MTNR1B variants on glucose metabolism and insulin secretion. PLoS One 5:e11761CrossRefPubMedCentralPubMed
21.
Zurück zum Zitat Hu C, Wang C, Zhang R et al (2010) Association of genetic variants of NOS1AP with type 2 diabetes in a Chinese population. Diabetologia 53:290–298CrossRefPubMed Hu C, Wang C, Zhang R et al (2010) Association of genetic variants of NOS1AP with type 2 diabetes in a Chinese population. Diabetologia 53:290–298CrossRefPubMed
22.
Zurück zum Zitat Wilkinson CP, Ferris FL 3rd, Klein RE et al (2003) Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales. Ophthalmology 110:1677–1682CrossRefPubMed Wilkinson CP, Ferris FL 3rd, Klein RE et al (2003) Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales. Ophthalmology 110:1677–1682CrossRefPubMed
23.
Zurück zum Zitat Purcell S, Neale B, Todd-Brown K et al (2007) PLINK: a toolset for whole-genome association and population-based linkage analysis. Am J Hum Genet 81:559–575CrossRefPubMedCentralPubMed Purcell S, Neale B, Todd-Brown K et al (2007) PLINK: a toolset for whole-genome association and population-based linkage analysis. Am J Hum Genet 81:559–575CrossRefPubMedCentralPubMed
24.
Zurück zum Zitat Hindorff LA, Sethupathy P, Junkins HA et al (2009) Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proc Natl Acad Sci U S A 106:9362–9367CrossRefPubMedCentralPubMed Hindorff LA, Sethupathy P, Junkins HA et al (2009) Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proc Natl Acad Sci U S A 106:9362–9367CrossRefPubMedCentralPubMed
25.
Zurück zum Zitat Yoshida K, Watanabe M, Hatakeyama S (2009) ZNRF1 interacts with tubulin and regulates cell morphogenesis. Biochem Biophys Res Commun 389:506–511CrossRefPubMed Yoshida K, Watanabe M, Hatakeyama S (2009) ZNRF1 interacts with tubulin and regulates cell morphogenesis. Biochem Biophys Res Commun 389:506–511CrossRefPubMed
26.
Zurück zum Zitat Wakatsuki S, Saitoh F, Araki T (2011) ZNRF1 promotes Wallerian degeneration by degrading AKT to induce GSK3B-dependent CRMP2 phosphorylation. Nat Cell Biol 13:1415–1423CrossRefPubMed Wakatsuki S, Saitoh F, Araki T (2011) ZNRF1 promotes Wallerian degeneration by degrading AKT to induce GSK3B-dependent CRMP2 phosphorylation. Nat Cell Biol 13:1415–1423CrossRefPubMed
27.
Zurück zum Zitat Hoxhaj G, Najafov A, Toth R, Campbell DG, Prescott AR, MacKintosh C (2012) ZNRF2 is released from membranes by growth factors and, together with ZNRF1, regulates the Na+/K+ATPase. J Cell Sci 125:4662–4675CrossRefPubMedCentralPubMed Hoxhaj G, Najafov A, Toth R, Campbell DG, Prescott AR, MacKintosh C (2012) ZNRF2 is released from membranes by growth factors and, together with ZNRF1, regulates the Na+/K+ATPase. J Cell Sci 125:4662–4675CrossRefPubMedCentralPubMed
28.
Zurück zum Zitat Nakamura K, Funakoshi H, Miyamoto K, Tokunaga F, Nakamura T (2001) Molecular cloning and functional characterization of a human scavenger receptor with C-type lectin (SRCL), a novel member of a scavenger receptor family. Biochem Biophys Res Commun 280:1028–1035CrossRefPubMed Nakamura K, Funakoshi H, Miyamoto K, Tokunaga F, Nakamura T (2001) Molecular cloning and functional characterization of a human scavenger receptor with C-type lectin (SRCL), a novel member of a scavenger receptor family. Biochem Biophys Res Commun 280:1028–1035CrossRefPubMed
29.
Zurück zum Zitat Jang S, Ohtani K, Fukuoh A et al (2009) Scavenger receptor collectin placenta 1 (CL-P1) predominantly mediates zymosan phagocytosis by human vascular endothelial cells. J Biol Chem 284:3956–3965CrossRefPubMed Jang S, Ohtani K, Fukuoh A et al (2009) Scavenger receptor collectin placenta 1 (CL-P1) predominantly mediates zymosan phagocytosis by human vascular endothelial cells. J Biol Chem 284:3956–3965CrossRefPubMed
30.
Zurück zum Zitat Yan J, Di Y, Shi H, Rao H, Huo K (2010) Overexpression of SCYL1-BP1 stabilizes functional p53 by suppressing MDM2-mediated ubiquitination. FEBS Lett 584:4319–4324CrossRefPubMedCentralPubMed Yan J, Di Y, Shi H, Rao H, Huo K (2010) Overexpression of SCYL1-BP1 stabilizes functional p53 by suppressing MDM2-mediated ubiquitination. FEBS Lett 584:4319–4324CrossRefPubMedCentralPubMed
31.
Zurück zum Zitat Hu L, Liu M, Chen L et al (2012) SCYL1 binding protein 1 promotes the ubiquitin-dependent degradation of Pirh2 and has tumor-suppressive function in the development of hepatocellular carcinoma. Carcinogenesis 33:1581–1588CrossRefPubMed Hu L, Liu M, Chen L et al (2012) SCYL1 binding protein 1 promotes the ubiquitin-dependent degradation of Pirh2 and has tumor-suppressive function in the development of hepatocellular carcinoma. Carcinogenesis 33:1581–1588CrossRefPubMed
32.
Zurück zum Zitat Yang ZP, Xie YH, Ling DY et al (2014) SCYL1BP1 has tumor-suppressive functions in human lung squamous carcinoma cells by regulating degradation of MDM2. Asian Pac J Cancer Prev 15:7467–7471CrossRefPubMed Yang ZP, Xie YH, Ling DY et al (2014) SCYL1BP1 has tumor-suppressive functions in human lung squamous carcinoma cells by regulating degradation of MDM2. Asian Pac J Cancer Prev 15:7467–7471CrossRefPubMed
33.
Zurück zum Zitat Morris EJ, Michaud WA, Ji JY, Moon NS, Rocco JW, Dyson NJ (2006) Functional identification of Api5 as a suppressor of E2F-dependent apoptosis in vivo. PLoS Genet 2:e196CrossRefPubMedCentralPubMed Morris EJ, Michaud WA, Ji JY, Moon NS, Rocco JW, Dyson NJ (2006) Functional identification of Api5 as a suppressor of E2F-dependent apoptosis in vivo. PLoS Genet 2:e196CrossRefPubMedCentralPubMed
34.
Zurück zum Zitat Cho H, Chung JY, Song KH et al (2014) Apoptosis inhibitor-5 overexpression is associated with tumor progression and poor prognosis in patients with cervical cancer. BMC Cancer 14:545CrossRefPubMedCentralPubMed Cho H, Chung JY, Song KH et al (2014) Apoptosis inhibitor-5 overexpression is associated with tumor progression and poor prognosis in patients with cervical cancer. BMC Cancer 14:545CrossRefPubMedCentralPubMed
Metadaten
Titel
Common variants in or near ZNRF1, COLEC12, SCYL1BP1 and API5 are associated with diabetic retinopathy in Chinese patients with type 2 diabetes
verfasst von
Danfeng Peng
Jie Wang
Rong Zhang
Feng Jiang
Shanshan Tang
Miao Chen
Jing Yan
Xue Sun
Shiyun Wang
Tao Wang
Dandan Yan
Yuqian Bao
Cheng Hu
Weiping Jia
Publikationsdatum
01.06.2015
Verlag
Springer Berlin Heidelberg
Erschienen in
Diabetologia / Ausgabe 6/2015
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-015-3569-9

Weitere Artikel der Ausgabe 6/2015

Diabetologia 6/2015 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.