Gender-stratified analysis of DLG5 R30Q in 4707 patients with Crohn disease and 4973 controls from 12 Caucasian cohorts

被引：41

作者：

Browning, B. L. ^{[1
,2
]}

Annese, V.

Barclay, M. L. ^{[3
,4
]}

Bingham, S. A. ^{[5
,6
]}

Brand, S. ^{[7
]}

Buening, C. ^{[8
]}

Castro, M.

Cucchiara, S. ^{[9
,10
]}

Dallapiccola, B. ^{[11
]}

Drummond, H. ^{[12
]}

Ferguson, L. R. ^{[1
]}

Ferraris, A. ^{[11
]}

Fisher, S. A. ^{[13
]}

Gearry, R. B. ^{[3
,4
]}

Glas, J. ^{[7
,14
]}

Henckaerts, L. ^{[15
]}

Huebner, C. ^{[1
]}

Knafelz, D. ^{[9
]}

Lakatos, L. ^{[16
]}

Lakatos, P. L. ^{[17
]}

Latiano, A. ^{[18
]}

Liu, X. ^{[19
,20
,21
,22
]}

Mathew, C.

Mueller-Myhsok, B. ^{[23
]}

Newman, W. G. ^{[24
]}

Nimmo, E. R. ^{[12
]}

Noble, C. L. ^{[12
]}

Palmieri, O. ^{[18
]}

Parkes, M. ^{[25
]}

Petermann, I.

Rutgeerts, P. ^{[15
]}

Satsangi, J.

Shelling, A. N. ^{[26
]}

Siminovitch, K. A. ^{[19
,20
,21
,22
]}

Toeroek, H.-P. ^{[27
]}

Tremelling, M. ^{[25
]}

Vermeire, S. ^{[15
]}

Valvano, M. R. ^{[18
]}

Witt, H. ^{[28
]}

机构：

[1] Univ Auckland, Discipline Nutr, Auckland 1, New Zealand

[2] Univ Auckland, Dept Stat, Auckland 1, New Zealand

[3] Christchurch Hosp, Dept Gastroenterol, Christchurch, New Zealand

[4] Christchurch Sch Med, Dept Med, Christchurch, New Zealand

[5] Univ Cambridge, EPIC Norfolk, Cambridge, England

[6] Univ Cambridge, MRC Ctr Nutr & Canc Prevent & Survival, Cambridge, England

[7] Univ Munich, Dept Med Grosshadern 2, Munich, Germany

[8] Univ Med Berlin, Charite, Dept Gastroenterol Hepatol & Endocrinol, Berlin, Germany

[9] Bambino Gesu Pediat Hosp, IRCCS, Gastroenterol Unit, Rome, Italy

[10] Univ Roma La Sapienza, Dept Pediat, Rome, Italy

[11] IRCCS, CSS Mendel Inst, Rome, Italy

[12] Univ Edinburgh, Western Gen Hosp, Gastrointestinal Unit, Edinburgh, Midlothian, Scotland

[13] Kings Coll London, Sch Med, Dept Med & Mol Genet, London WC2R 2LS, England

[14] Univ Munich, Dept Restorat Dent & Periodontol, Munich, Germany

[15] Univ Hosp Gasthuisberg, Dept Gastroenterol, Louvain, Belgium

[16] Csolnoky F Cty Hosp, Dept Med 1, Veszprem, Hungary

[17] Semmelweis Univ, Dept Med 1, H-1085 Budapest, Hungary

[18] IRCCS, Dept Gastroenterol, San Giovanni Rotondo, Italy

[19] Univ Toronto, Dept Med, Toronto, ON, Canada

[20] Univ Toronto, Dept Immunol, Toronto, ON, Canada

[21] Univ Toronto, Dept Med Genet & Microbiol, Toronto, ON, Canada

[22] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada

[23] Max Planck Inst Psychiat, D-80804 Munich, Germany

[24] Univ Manchester, Dept Med Genet, Manchester, Lancs, England

[25] Addenbrookes Hosp, Dept Gastroenterol, Cambridge CB2 2QQ, England

[26] Univ Auckland, Dept Obstet & Gynaecol, Auckland 1, New Zealand

[27] Univ Munich, Dept Surg Innenstadt, Munich, Germany

[28] Univ Med Berlin, Dept Pediat, Charite, Berlin, Germany

来源：

JOURNAL OF MEDICAL GENETICS | 2008年 / 45卷 / 01期

基金：

英国医学研究理事会;

关键词：

D O I：

10.1136/jmg.2007.050773

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Background: DLG5 p. R30Q has been reported to be associated with Crohn disease ( CD), but this association has not been replicated in most studies. A recent analysis of gender-stratified data from two case-control studies and two population cohorts found an association of DLG5 30Q with increased risk of CD in men but not in women and found differences between 30Q population frequencies for males and females. Male-female differences in population allele frequencies and male-specific risk could explain the difficulty in replicating the association with CD. Methods: DLG5 R30Q genotype data were collected for patients with CD and controls from 11 studies that did not include gender-stratified allele counts in their published reports and tested for male-female frequency differences in controls and for case-control frequency differences in men and in women. Results: The data showed no male-female allele frequency differences in controls. An exact conditional test gave marginal evidence that 30Q is associated with decreased risk of CD in women (p= 0.049, OR= 0.87, 95% CI 0.77 to 1.00). There was also a trend towards reduced 30Q frequencies in male patients with CD compared with male controls, but this was not significant at the 0.05 level (p = 0.058, OR= 0.87, 95% CI 0.74 to 1.01). When data from this study were combined with previously published, gender-stratified data, the 30Q allele was found to be associated with decreased risk of CD in women (p= 0.010, OR= 0.86, 95% CI 0.76 to 0.97), but not in men. Conclusion: DLG5 30Q is associated with a small reduction in risk of CD in women.

引用

页码：36 / 42

页数：7

共 49 条

[1] A haplotype map of the human genome [J].

Altshuler, D ;

Brooks, LD ;

Chakravarti, A ;

Collins, FS ;

Daly, MJ ;

Donnelly, P ;

Gibbs, RA ;

Belmont, JW ;

Boudreau, A ;

Leal, SM ;

Hardenbol, P ;

Pasternak, S ;

Wheeler, DA ;

Willis, TD ;

Yu, FL ;

Yang, HM ;

Zeng, CQ ;

Gao, Y ;

Hu, HR ;

Hu, WT ;

Li, CH ;

Lin, W ;

Liu, SQ ;

Pan, H ;

Tang, XL ;

Wang, J ;

Wang, W ;

Yu, J ;

Zhang, B ;

Zhang, QR ;

Zhao, HB ;

Zhao, H ;

Zhou, J ;

Gabriel, SB ;

Barry, R ;

Blumenstiel, B ;

Camargo, A ;

Defelice, M ;

Faggart, M ;

Goyette, M ;

Gupta, S ;

Moore, J ;

Nguyen, H ;

Onofrio, RC ;

Parkin, M ;

Roy, J ;

Stahl, E ;

Winchester, E ;

Ziaugra, L ;

Shen, Y .

NATURE, 2005, 437 (7063) :1299-1320

[2]

[Anonymous], 2006, R LANG ENV STAT COMP

[3] DLG5 R30Q variant is a female-specific protective factor in pediatric onset Crohn's disease [J].

Biank, Vincent ;

Friedrichs, Frauke ;

Babusukumar, Umesh ;

Wang, Tao ;

Stoll, Monika ;

Broeckel, Ulrich ;

Kugathasan, Subra .

AMERICAN JOURNAL OF GASTROENTEROLOGY, 2007, 102 (02) :391-398

[4]

Binder V, 2004, BEST PRACT RES CL GA, V18, P463, DOI [10.1016/j.bpg.2003.12.002, 10.1016/j.bpg.2003.13.002]

[5] Association of DLG5 variants with inflammatory bowel disease in the New Zealand Caucasian population and meta-analysis of the DLG5 R30Q variant [J].

Browning, Brian L. ;

Huebner, Claudia ;

Petermann, Ivonne ;

Dernmers, Pieter ;

McCulloch, Alan ;

Georry, Richard B. ;

Barclay, Murray L. ;

Shelling, Andrew N. ;

Ferguson, Lynnette R. .

INFLAMMATORY BOWEL DISEASES, 2007, 13 (09) :1069-1076

[6] DLG5 variants in inflammatory bowel disease [J].

Büning, C ;

Geerdts, L ;

Fiedler, T ;

Gentz, E ;

Pitre, G ;

Reuter, W ;

Luck, W ;

Buhner, S ;

Molnar, T ;

Nagy, F ;

Lonovics, J ;

Dignass, A ;

Landt, F ;

Nickel, R ;

Genschel, J ;

Lochs, H ;

Schmidt, HHJ ;

Witt, H .

AMERICAN JOURNAL OF GASTROENTEROLOGY, 2006, 101 (04) :786-792

[7] 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

[8] THE COMBINATION OF ESTIMATES FROM DIFFERENT EXPERIMENTS [J].

COCHRAN, WG .

BIOMETRICS, 1954, 10 (01) :101-129

[9] Risk of inflammatory bowel disease attributable to smoking, oral contraception and breastfeeding in Italy:: a nationwide case-control study [J].

Corrao, G ;

Tragnone, A ;

Caprilli, R ;

Trallori, G ;

Papi, C ;

Andreoli, A ;

Di Paolo, M ;

Riegler, G ;

Rigo, GP ;

Ferraù, O ;

Mansi, C ;

Ingrosso, M ;

Valpiani, D .

INTERNATIONAL JOURNAL OF EPIDEMIOLOGY, 1998, 27 (03) :397-404

[10] Role of CARD15, DLG5 and OCTN genes polymorphisms in children with inflammatory bowel diseases [J].

Cucchiara, S. ;

Latiano, A. ;

Palmieri, O. ;

Staiano, A. M. ;

D'Inca, R. ;

Guariso, G. ;

Vieni, G. ;

Rutigliano, V. ;

Borrelli, O. ;

Valvano, M. R. ;

Annese, V. .

WORLD JOURNAL OF GASTROENTEROLOGY, 2007, 13 (08) :1221-1229

← 1 2 3 4 5 →