Heterogeneity in gene loci associated with type 2 diabetes on human chromosome 20q13.1

被引：30

作者：

Bento, J. L. ^{[2
,3
]}

Palmer, N. D. ^{[2
,3
]}

Zhong, M. ^{[3
]}

Roh, B. ^{[2
,3
]}

Lewis, J. P. ^{[3
]}

Wing, M. R. ^{[3
]}

Pandya, H.

Freedman, B. I. ^{[4
]}

Langefeld, C. D. ^{[5
]}

Rich, S. S. ^{[1
]}

Bowden, D. W. ^{[2
,3
]}

Mychaleckyj, J. C. ^{[1
]}

机构：

[1] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA 22902 USA

[2] Wake Forest Univ, Sch Med, Dept Biochem, Winston Salem, NC 27157 USA

[3] Wake Forest Univ, Sch Med, Ctr Human Genome, Winston Salem, NC 27157 USA

[4] Wake Forest Univ, Sch Med, Dept Internal Med, Winston Salem, NC 27157 USA

[5] Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27157 USA

来源：

GENOMICS | 2008年 / 92卷 / 04期

关键词：

type; 2; diabetes; end-stage renal disease; SNPs; chromosome; 20; linkage disequilibrium; haplotypes; association; heterogeneity;

D O I：

10.1016/j.ygeno.2008.06.004

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Human chromosome 20q12-q13.1 has been linked to type 2 diabetes mellitus (T2DM) in multiple studies. We screened a 5.795-Mb region for diabetes-related susceptibility genes in a Caucasian cohort of 310 controls and 300 cases with T2DM and end-stage renal disease (ESRD), testing 390 SNPs for association with T2DM-ESRD. The most significant SNPs were found in the perigenic regions: HNF4A (hepatocyte nuclear factor 4), SLC12A5 (potassium-chloride cotransporter member 5), CDH22 (cadherin-like 22), ELMO2 (engulfment and cell motility 2), SLC13A3 (sodium-dependent dicarboxylate transporter member 3), and PREX1 (phosphatidylinositol 3,4,5-triphosphate-dependent RAC exchanger 1). Haplotype analysis found six haplotype blocks globally associated with disease (p < 0.05). We replicated the PREX1 SNP association in an independent case-control T2DM population and inferred replication of CDH22, ELMO2, SLC13A3, SLC12A5, and PREX1 using in silico perigenic analysis of two T2DM Genome-Wide Association Study data sets. We found substantial heterogeneity between study results. (C) 2008 Elsevier Inc. All rights reserved.

引用

页码：226 / 234

页数：9

共 48 条

[1] The common PPARγ Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes [J].

Altshuler, D ;

Hirschhorn, JN ;

Klannemark, M ;

Lindgren, CM ;

Vohl, MC ;

Nemesh, J ;

Lane, CR ;

Schaffner, SF ;

Bolk, S ;

Brewer, C ;

Tuomi, T ;

Gaudet, D ;

Hudson, TJ ;

Daly, M ;

Groop, L ;

Lander, ES .

NATURE GENETICS, 2000, 26 (01) :76-80

[2] Genetic analysis of HNF4A polymorphisms in Caucasian-American type 2 diabetes [J].

Bagwell, AM ;

Bento, JL ;

Mychaleckyj, JC ;

Freedman, BI ;

Langefeld, CD ;

Bowden, DW .

DIABETES, 2005, 54 (04) :1185-1190

[3] Comparative genomic analysis of the HNF-4α transcription factor gene [J].

Bagwell, AM ;

Bailly, A ;

Mychaleckyj, JC ;

Freedman, BI ;

Bowden, DW .

MOLECULAR GENETICS AND METABOLISM, 2004, 81 (02) :112-121

[4] Identification of basolateral membrane targeting signal of human sodium-dependent dicarboxylate transporter 3 [J].

Bai, XY ;

Chen, XM ;

Feng, Z ;

Hou, K ;

Zhang, P ;

Fu, B ;

Shi, SZ .

JOURNAL OF CELLULAR PHYSIOLOGY, 2006, 206 (03) :821-830

[5] Haploview: analysis and visualization of LD and haplotype maps [J].

Barrett, JC ;

Fry, B ;

Maller, J ;

Daly, MJ .

BIOINFORMATICS, 2005, 21 (02) :263-265

[6]

BEAULIEU M, 2004, MULTIPLEXING HOMOGEN

[7] Genetic analysis of the GLUT10 glucose transporter (SLC2A10) polymorphisms in Caucasian American type 2 diabetes -: art. no. 42 [J].

Bento, JL ;

Bowden, DW ;

Mychaleckyj, JC ;

Hirakawa, S ;

Rich, SS ;

Freedman, BI ;

Segade, F .

BMC MEDICAL GENETICS, 2005, 6

[8] Association of protein tyrosine phosphatase 1B gene polymorphisms with type 2 diabetes [J].

Bento, JL ;

Palmer, ND ;

Mychaleckyj, JC ;

Lange, LA ;

Langefeld, CD ;

Rich, SS ;

Freedman, BI ;

Bowden, DW .

DIABETES, 2004, 53 (11) :3007-3012

[9] Linkage of genetic markers on human chromosomes 20 and 12 to NIDDM in Caucasian sib pairs with a history of diabetic nephropathy [J].

Bowden, DW ;

Sale, M ;

Howard, TD ;

Qadri, A ;

Spray, BJ ;

Rothschild, CB ;

Akots, G ;

Rich, SS ;

Freedman, BI .

DIABETES, 1997, 46 (05) :882-886

[10] Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls [J].

Burton, Paul R. ;

Clayton, David G. ;

Cardon, Lon R. ;

Craddock, Nick ;

Deloukas, Panos ;

Duncanson, Audrey ;

Kwiatkowski, Dominic P. ;

McCarthy, Mark I. ;

Ouwehand, Willem H. ;

Samani, Nilesh J. ;

Todd, John A. ;

Donnelly, Peter ;

Barrett, Jeffrey C. ;

Davison, Dan ;

Easton, Doug ;

Evans, David ;

Leung, Hin-Tak ;

Marchini, Jonathan L. ;

Morris, Andrew P. ;

Spencer, Chris C. A. ;

Tobin, Martin D. ;

Attwood, Antony P. ;

Boorman, James P. ;

Cant, Barbara ;

Everson, Ursula ;

Hussey, Judith M. ;

Jolley, Jennifer D. ;

Knight, Alexandra S. ;

Koch, Kerstin ;

Meech, Elizabeth ;

Nutland, Sarah ;

Prowse, Christopher V. ;

Stevens, Helen E. ;

Taylor, Niall C. ;

Walters, Graham R. ;

Walker, Neil M. ;

Watkins, Nicholas A. ;

Winzer, Thilo ;

Jones, Richard W. ;

McArdle, Wendy L. ;

Ring, Susan M. ;

Strachan, David P. ;

Pembrey, Marcus ;

Breen, Gerome ;

St Clair, David ;

Caesar, Sian ;

Gordon-Smith, Katherine ;

Jones, Lisa ;

Fraser, Christine ;

Green, Elain K. .

NATURE, 2007, 447 (7145) :661-678

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