Role of discs large homolog 5

Table 1 Summary of genetic studies that analyzed DLG5 variants for their association to IBD or CD

Study		Summary of results	Countryof samplecollection	Number ofparticipants	Detailedresults	Further sampleinfo:gender/age
Association findings	Stoll et al 2004[1]	First finding of association between DLG5 variants and IBD/CD Positive association between R30Q (haplotype D tagging SNP) and IBD/CD Negative association between haplotype A and IBD/CD Positive association between P1371Q (rare haplotype) and IBD/CD Interaction between R30Q variant and CARD15 risk alleles	Germany	457 IBD trios (302 CD)	TDT (T:U) single SNPs R30Q IBD: 92:64, P = 0.025; CD: 60:42, P = 0.075 Haplotype A (DLG5_e26) IBD: 162:225, P = 0.001; CD: 108:151, P = 0.008 P1371Q IBD: 40:24, P = 0.046; CD: 24:17, NS	Controls age and sex matched
			Germany, United Kingdom	1 Replication: 485 IBD trios (271 CD)	TDT (T:U) single SNPs R30Q IBD: 90:73, P = 0.09; CD: 58:43, P = 0.065 Haplotype A (DLG5_e26) IBD: 165:214, P = 0.006
			Northern Europe	2 Replication: 538 CD patients, 548 controls	Allele frequencies (cases versus controls) R30Q CD: 13.2 %, controls: 9%, OR = 1.62, P = 0.001 HaplotypeA CD: 32.4 %, controls: 36.1%, OR=0.74, P = 0.01 P1371Q CD: 4.2 %, controls: 2.5%, OR=1.51, P = 0.01
	Daly et al 2005[7]	Replication of positive association between R30Q and CD in two of three independent study samples No replication of negative association between haplotype A and CD P1371Q variant not polymorphic	Canada, Italy	249 CD patients, 207 controls	Allele frequencies (cases versus controls) R30Q CD: 11%, controls: 5.9%, χ2 = 7.8, P = 0.003 Haplotype A CD: 36.5%, controls: 40.1 %, χ2 = 1.4, P = 0.12 P1371Q Not polymorphic
			United Kingdom	353 CD patients, 336 UC patients, 493 controls	Allele frequencies (cases versus controls) R30Q CD: 9.3%, controls: 9.7%, NS Haplotype A CD: 34%, controls: 35.7%, NS
			Canada, United Kingdom	306 IBD trios (88 % CD)	TDT (observed:expected transmissions) R30Q IBD: 76:65.1, P = 0.018 Haplotype A IBD: 304: 307.8, NS
	Newman et al 2006[25]	Non replication of positive association between R30Q variant and IBD/CD Association between haplotype A and IBD/CD, however positive association in this study instead of negative Replication of positive association between P1371Q and IBD/CD	Canada	402 CD patients, 179 UC patients, 537 controls	Allele frequencies (cases versus controls) R30Q Controls: 8.7 %; IBD: 8.2 %, NS; CD: 7.8 %, NS Haplotype A Controls: 30.8 %; IBD: 36.1 %, P = 0.01; CD: 36.6 %, P = 0.01 P1371Q Controls: 6.1 %; IBD: 9.6%, P = 0.01; CD: 10.3%, P = 0.01 Frequencies for both variants did not differ between males and females in the cases and controls	Mean age CD patients: 20.4 yr Controls: 31 yr
Non replication findings	Török et al 2005[26]	Non replication of positive association between R30Q and IBD/CD Non replication of negative association between haplotype A and IBD/CD Non replication of positive association between P1371Q and IBD/CD Non replication of interaction between R30Q variant and CARD15 risk alleles	Southern Germany	625 CD patients, 363 UC patients, 1012 controls	Allele frequencies (cases versus controls) R30Q Controls: 10.8%; IBD: 10.1%, NS; CD: 9.8%, NS Haplotype A Controls: 35.2%; IBD: 34.4%, NS; CD: 34.6%, NS P1371Q Controls: 4.4%; IBD: 4.5%, NS; CD: 3.9%, NS	Controls age and sex matched
	Noble et al 2006[8]	Non replication of positive association between R30Q and IBD/CD Non replication of negative association between haplotype A and IBD/CD Non replication of interaction between R30Q variant and CARD15 risk alleles	Scotland	374 CD patients, 305 UC patients, 294 controls	Allele frequencies (cases versus controls) R30Q Controls: 13.2%; IBD: 11.4%, P = NS; CD: 11.4 %, NS Haplotype A Controls: 31.5 %; IBD: 35 %, P = 0.17; CD: 36.9 %, P = 0.078	Numbers Male/female (median age) CD patients: 181/193 (28 yr) Controls: 143/151 (39 yr)
	Vermeire et al 2005[24]	Non replication of positive association between R30Q and IBD/CD Non replication of negative association between haplotype A and IBD/CD Replication of interaction between R30Q variant and CARD15 risk alleles	Belgium	373 IBD trios (80 % CD)	TDT (T:U) single SNPs R30Q IBD: 51:79, P = 0.01; CD: 42:71, P = 0.01 Haplotype A (DLG5_e26) IBD: 161:149, NS; CD: 134:123, NS	Numbers Male/female (mean age) IBD patients: 162/211 (37 yr)
				472 CD patients, 120 UC patients, 305 controls	Allele frequencies (cases versus controls) R30Q Controls: 10.8%; IBD: 11.8%, NS; CD: 11.5%, NS Haplotype A Controls: 33.8 %; IBD: 33.9 %, NS; CD: 35.2 %, NS	IBD patients: 256/352 (45 yr) Controls: 139/166 (41 yr)
R30Q not polymorphic	Yamazaki et al 2004[4]	R30Q polymorphism not polymorphic in Japanese patients Non replication of negative association between haplotype A and CD Non replication of positive association between P1371Q and CD Other DLG5 variant risk associated instead	Japan	484 CD patients, 345 controls	Allele frequencies (cases versus controls) R30Q Polymorphism absent in 48 Japanese patients tested Haplotype A CD: 24.6 %, controls: 22%, NS P1371Q CD: 16.5%, controls: 19.2%, NS DLG5 SNP rs3758462 CD: 18.5 %, controls: 22.1%, P = 0.068 (P = 0.023, additive inheritance model for rare variant)
	Gazouli et al 2005[11]	R30Q polymorphism absent in Greek study sample	Greece	120 CD patients, 85 UC patients, 100 controls	R30Q Polymorphism absent
R30Q gender specificity	Friedrichs et al 2006[15]	Gender specific analysis of R30Q polymor-phism in German, Italian and Canadian study samples with positive association findings[1,7] R30Q confers susceptibility to CD in males but not females Observation of possible transmission ratio distortion (TRD) in general population TRD confirmed by two independent population based samples, one of which was a birth cohort	Germany, Italy, Canada	613 CD patients, 749 controls	Allele frequencies (cases versus controls) R30Q Q allele frequencies male CD patients: 10.1%, male controls: 5.2% ORmales = 2.5, 95% confidence interval = 1.5-4.1, P < 0.001 female CD patients: 10.9%, female controls: 11.3% ORfemales = 1, NS TRD Q allele frequencies newborn study sample males: 7.1%, females: 11%	Numbers Male/female (mean age) CD patients: 235/375 (36 yr) Controls: 403/346 (40 yr)

TDT: Transmission disequilibrium test; T:U: Transmitted alleles versus untransmitted alleles (transmissions from heterozygous parents to affected offspring); OR : Odds ratio; NS: Not significant.