Low alpha-defensin gene copy number increases the risk for IgA nephropathy development and poor renal survival

Zhen Ai; Ming Li; Wenting Liu; Jia-Nee Foo; Omniah Mansouri; Peiran Yin; Qian Zhou; Xueqing Tang; Xiuqing Dong; Shaozhen Feng; Ricong Xu; Zhong Zhong; Jian Chen; Jianxin Wan; Tanqi Lou; Jianwen Yu; Qin Zhou; Jinjin Fan; Haiping Mao; Daniel GalUCL; Jonathan Barratt; John AL Armour; Jianjun Liu; Xueqing Yu

Chinese︱Feedback︱Save this page

Low alpha-defensin gene copy number increases the risk for IgA nephropathy development and poor renal survival

Zhen Ai 1,Ming Li 1 #,Wenting Liu 1,Jia-Nee Foo 2,Omniah Mansouri 3,Peiran Yin 1,Qian Zhou 1,Xueqing Tang 1,Xiuqing Dong 1,Shaozhen Feng 1,Ricong Xu 1,Zhong Zhong 1,Jian Chen 4,Jianxin Wan 5,Tanqi Lou 6,Jianwen Yu 1,Qin Zhou 1,Jinjin Fan 1,Haiping Mao 1,Daniel GalUCL 7,Jonathan Barratt 8,John AL Armour 9,Jianjun Liu 2,Xueqing Yu 1 *

1.Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510080, China

2.Human Genetics, Genome Institute of Singapore, Singapore 138672, Singapore. 4School of Life Sciences, University Jia-Nee Foo Human Genetics, Genome Institute of Singapore, Singapore 138672, Singapore

3. School of Life Sciences, University of Nottingham, Queen’s Medical Centre, Nottingham NG7 2UH, UK

4. Department of Nephrology, Fuzhou General Hospital of Nanjing Military Command, Fuzhou, Fujian 350025, China

5. Department of Nephrology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, China

6.Department of Nephrology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, China

7.Centre for Nephrology, Royal Free Hospital, London, NW3 2PF, UK

8.Department of Infection, Immunity and Inflammation, University of Leicester, Leicester LE1 9HN, UK.

9.School of Life Sciences, University of Nottingham, Queen’s Medical Centre, Nottingham NG7 2UH, UK

*Correspondence author

#Submitted by

Subject:

Funding: grant from the BBSRC (BB/1006370/1) to JALA, and the Agency for Science & Technology and Research (A*STAR) of Sing（No. ）, Yong Scholars Fund for the Doctoral Program of Higher Education of China（No.20120171120087）, Guangdong Department of Science & Technology Translational Medicine Center grant （No.2011A080300002）, Guangzhou Committee of Science and Technology, China（No.2012J5100031）, OM is supported by the Division of Higher Education, Kingdom of Saudi Arabia（No.S4674）, Young Scientists Fund of National Natural Science Foundation of China（No.81200489）, the Science and Technology Planning Project of Guangdong Province, China（No.2013B051000019）, the Specialized Research Fund for the Doctoral Program of Higher Education of China（No.20130171130008）

Opened online: 3 May 2017

Accepted by: none

Citation: Zhen Ai,Ming Li,Wenting Liu.Low alpha-defensin gene copy number increases the risk for IgA nephropathy development and poor renal survival[OL]. [ 3 May 2017] http://en.paper.edu.cn/en_releasepaper/content/4726898

IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Although being a major source of genetic variation, copy number variations (CNVs) are poorly studied for their involvement in disease development. Here we performed association analysis of DEFA1A3 CNV locus in two independent IgAN cohorts of Southern Chinese Han (total 1189 cases and 1187 healthy controls). We discovered three independent copy number associations within the locus: DEFA1A3 (P=3.99×10-9, OR=0.88), DEFA3 (P=6.55×10-5, OR=0.82) and a noncoding deletion variant (211bp) (P=3.50×10-16, OR=0.75) (OR per copy, fixed-effects meta-analysis). While showing strong association with increased risk for IgAN (P=9.56×10-20), low total copy numbers of the three variants also showed significant association with poor long-term renal survival of IgAN (P=0.03, HR=3.69, after controlling the effects of known prognostic factors) as well as the high serum IgA1 level (P=0.02) and high proportion of galactose-deficient IgA1 (P=0.03). As replication, we confirmed the associations of DEFA1A3 (P=4.42×10-4, OR=0.82) and DEFA3 copy numbers (P=4.30×10-3, OR=0.74) with IgAN in a Caucasian cohort (531 cases and 198controls) and found 211bp variant to be extremely rare in Caucasians. Interestingly, we also observed an association of 211bp copy number with membranous nephropathy (P=1.11×10-7, OR=0.74 in 493 Chinese cases and 500 matched controls), but not with diabetic kidney disease (in 806 Chinese cases and 786 matched controls). By explaining 4.96% of risk variance (the strongest genetic susceptibility locus so far) and influencing the renal progression of IgAN, the DEFA1A3 CNV locus is a potential candidate of novel therapeutic target and prognostic biomarker.

Keywords:IgA nephropathy; DEFA; genome-wide association studies

For this paper

● PDF (0B)
● Revision 0 　　
● Print this paper
● Recommend this paper to a friend
● Add to my favorite list

Saved Papers

Please enter a name for this paper to be shown in your personalized Saved Papers list

Tags

Add yours

Related Papers

Statistics

PDF Downloaded	71
Bookmarked	0
Recommend	0
Comments	Array

Submit your papers

Alert Name:
Alerting to:
Authentication email will be sent to your email address in 24 hours
Frequency:
Email Message Format:	Plain text Graphical(HTML)

Complete the form below and we will recommend the selected titles to your friends on your behalf. * Indicates a required field.
Your name*:
Your email address*:
Recipient's name*:
Recipient's email address*:
(multiple recipient's names and email addresses should be separated with semicolons)
Your comments:	I thought you would find the page(s) useful.

Your name:
Your email address:
Recipient's name:
Recipient's email address:
(multiple recipient's names and email addresses should be separated with semicolons)
Your comments:	I thought you would find this page useful.

Disclaimer: This message was sent to your friend using the "Send it to a friend" facility on the Sciencepaper Online’ WWW site, http://www.paper.edu.cn/en. The Sciencepaper Online is not responsible for the content of this email, and anything said in this email does not necessarily reflect the Sciencepaper Online's views.

	Check out RSS, or use RSS reader to subscribe this item

Saved Papers