Diverticulitis and Crohn's disease have distinct but overlapping tumor necrosis superfamily 15 haplotypes

Tara M. Connelly, Christine S. Choi, Arthur Berg, Leonard Harris, Joel Coble, Walter Koltun

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background Diverticulitis (DD) and Crohn's disease (CD) have overlapping features including bowel structuring, inflammation, and infection. Tumor necrosis superfamily 15 (TNFSF15) is an immunoregulatory, anti-angiogenic gene. CD has been previously associated with a haplotype of five TNFSF15 single-nucleotide polymorphism alleles: rs3810936 (G allele), rs6478108 (A), rs6478109 (G), rs7848647 (G), and rs7869487 (A). We aimed to determine the TNFSF15 risk haplotype for DD versus controls with a subgroup analysis of youthful DD patients (aged ≤55 y) versus older controls (aged ≥55 y). Methods A total of 148 diverticulitis patients (90 aged ≤55 y) and 200 controls (87 aged ≥55 y) were genotyped using our custom-designed Illumina Veracode microarray chip. Genotypes from rs3810936, rs6478108, rs6478109, rs7848647, rs7869487 and two additional TNFSF15 single nucleotide polymorphisms, rs3810936 and rs11554257, were analyzed. PHASE version 2.1, R with HaploStats and the Broad Institute's Haploview program were used for statistics and imputed haplotype frequency. Permutation corrected for multiple comparisons. Results The CD GAGGA haplotype was significantly associated with diverticulitis (P = 0.03) in the all DD versus all controls comparison. A second haplotype, rs6478108 (A), rs6478109 (G), rs7869487 (A), and rs4263839 (G), was also associated with DD in this cohort (P = 0.025). A third haplotype rs6478108 (A), rs6478109 (G), rs7848647 (G) and rs7869487 (A), rs4263839 (G) was demonstrated in the DD < 55 versus controls >55 comparison (P = 0.045). Conclusions Distinct but overlapping TNFSF15 haplotypes were demonstrated in diverticulitis patients versus healthy controls when compared with the known Crohn's risk haplotype suggesting similar but distinct genetic predispositions. This study strengthens the role for a genetic predisposition to diverticulitis that involves the TNFSF15 gene.

Original languageEnglish (US)
Pages (from-to)262-269
Number of pages8
JournalJournal of Surgical Research
Volume214
DOIs
StatePublished - Jun 15 2017

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Diverticulitis
Crohn Disease
Haplotypes
Necrosis
Neoplasms
Genetic Predisposition to Disease
Single Nucleotide Polymorphism
Alleles
Genes
Genotype
Inflammation
Infection

All Science Journal Classification (ASJC) codes

  • Surgery

Cite this

Connelly, Tara M. ; Choi, Christine S. ; Berg, Arthur ; Harris, Leonard ; Coble, Joel ; Koltun, Walter. / Diverticulitis and Crohn's disease have distinct but overlapping tumor necrosis superfamily 15 haplotypes. In: Journal of Surgical Research. 2017 ; Vol. 214. pp. 262-269.
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abstract = "Background Diverticulitis (DD) and Crohn's disease (CD) have overlapping features including bowel structuring, inflammation, and infection. Tumor necrosis superfamily 15 (TNFSF15) is an immunoregulatory, anti-angiogenic gene. CD has been previously associated with a haplotype of five TNFSF15 single-nucleotide polymorphism alleles: rs3810936 (G allele), rs6478108 (A), rs6478109 (G), rs7848647 (G), and rs7869487 (A). We aimed to determine the TNFSF15 risk haplotype for DD versus controls with a subgroup analysis of youthful DD patients (aged ≤55 y) versus older controls (aged ≥55 y). Methods A total of 148 diverticulitis patients (90 aged ≤55 y) and 200 controls (87 aged ≥55 y) were genotyped using our custom-designed Illumina Veracode microarray chip. Genotypes from rs3810936, rs6478108, rs6478109, rs7848647, rs7869487 and two additional TNFSF15 single nucleotide polymorphisms, rs3810936 and rs11554257, were analyzed. PHASE version 2.1, R with HaploStats and the Broad Institute's Haploview program were used for statistics and imputed haplotype frequency. Permutation corrected for multiple comparisons. Results The CD GAGGA haplotype was significantly associated with diverticulitis (P = 0.03) in the all DD versus all controls comparison. A second haplotype, rs6478108 (A), rs6478109 (G), rs7869487 (A), and rs4263839 (G), was also associated with DD in this cohort (P = 0.025). A third haplotype rs6478108 (A), rs6478109 (G), rs7848647 (G) and rs7869487 (A), rs4263839 (G) was demonstrated in the DD < 55 versus controls >55 comparison (P = 0.045). Conclusions Distinct but overlapping TNFSF15 haplotypes were demonstrated in diverticulitis patients versus healthy controls when compared with the known Crohn's risk haplotype suggesting similar but distinct genetic predispositions. This study strengthens the role for a genetic predisposition to diverticulitis that involves the TNFSF15 gene.",
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Diverticulitis and Crohn's disease have distinct but overlapping tumor necrosis superfamily 15 haplotypes. / Connelly, Tara M.; Choi, Christine S.; Berg, Arthur; Harris, Leonard; Coble, Joel; Koltun, Walter.

In: Journal of Surgical Research, Vol. 214, 15.06.2017, p. 262-269.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Diverticulitis and Crohn's disease have distinct but overlapping tumor necrosis superfamily 15 haplotypes

AU - Connelly, Tara M.

AU - Choi, Christine S.

AU - Berg, Arthur

AU - Harris, Leonard

AU - Coble, Joel

AU - Koltun, Walter

PY - 2017/6/15

Y1 - 2017/6/15

N2 - Background Diverticulitis (DD) and Crohn's disease (CD) have overlapping features including bowel structuring, inflammation, and infection. Tumor necrosis superfamily 15 (TNFSF15) is an immunoregulatory, anti-angiogenic gene. CD has been previously associated with a haplotype of five TNFSF15 single-nucleotide polymorphism alleles: rs3810936 (G allele), rs6478108 (A), rs6478109 (G), rs7848647 (G), and rs7869487 (A). We aimed to determine the TNFSF15 risk haplotype for DD versus controls with a subgroup analysis of youthful DD patients (aged ≤55 y) versus older controls (aged ≥55 y). Methods A total of 148 diverticulitis patients (90 aged ≤55 y) and 200 controls (87 aged ≥55 y) were genotyped using our custom-designed Illumina Veracode microarray chip. Genotypes from rs3810936, rs6478108, rs6478109, rs7848647, rs7869487 and two additional TNFSF15 single nucleotide polymorphisms, rs3810936 and rs11554257, were analyzed. PHASE version 2.1, R with HaploStats and the Broad Institute's Haploview program were used for statistics and imputed haplotype frequency. Permutation corrected for multiple comparisons. Results The CD GAGGA haplotype was significantly associated with diverticulitis (P = 0.03) in the all DD versus all controls comparison. A second haplotype, rs6478108 (A), rs6478109 (G), rs7869487 (A), and rs4263839 (G), was also associated with DD in this cohort (P = 0.025). A third haplotype rs6478108 (A), rs6478109 (G), rs7848647 (G) and rs7869487 (A), rs4263839 (G) was demonstrated in the DD < 55 versus controls >55 comparison (P = 0.045). Conclusions Distinct but overlapping TNFSF15 haplotypes were demonstrated in diverticulitis patients versus healthy controls when compared with the known Crohn's risk haplotype suggesting similar but distinct genetic predispositions. This study strengthens the role for a genetic predisposition to diverticulitis that involves the TNFSF15 gene.

AB - Background Diverticulitis (DD) and Crohn's disease (CD) have overlapping features including bowel structuring, inflammation, and infection. Tumor necrosis superfamily 15 (TNFSF15) is an immunoregulatory, anti-angiogenic gene. CD has been previously associated with a haplotype of five TNFSF15 single-nucleotide polymorphism alleles: rs3810936 (G allele), rs6478108 (A), rs6478109 (G), rs7848647 (G), and rs7869487 (A). We aimed to determine the TNFSF15 risk haplotype for DD versus controls with a subgroup analysis of youthful DD patients (aged ≤55 y) versus older controls (aged ≥55 y). Methods A total of 148 diverticulitis patients (90 aged ≤55 y) and 200 controls (87 aged ≥55 y) were genotyped using our custom-designed Illumina Veracode microarray chip. Genotypes from rs3810936, rs6478108, rs6478109, rs7848647, rs7869487 and two additional TNFSF15 single nucleotide polymorphisms, rs3810936 and rs11554257, were analyzed. PHASE version 2.1, R with HaploStats and the Broad Institute's Haploview program were used for statistics and imputed haplotype frequency. Permutation corrected for multiple comparisons. Results The CD GAGGA haplotype was significantly associated with diverticulitis (P = 0.03) in the all DD versus all controls comparison. A second haplotype, rs6478108 (A), rs6478109 (G), rs7869487 (A), and rs4263839 (G), was also associated with DD in this cohort (P = 0.025). A third haplotype rs6478108 (A), rs6478109 (G), rs7848647 (G) and rs7869487 (A), rs4263839 (G) was demonstrated in the DD < 55 versus controls >55 comparison (P = 0.045). Conclusions Distinct but overlapping TNFSF15 haplotypes were demonstrated in diverticulitis patients versus healthy controls when compared with the known Crohn's risk haplotype suggesting similar but distinct genetic predispositions. This study strengthens the role for a genetic predisposition to diverticulitis that involves the TNFSF15 gene.

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