Surgical Diverticulitis Associated with TNFSF15 Gene Single Nucleotide Polymorphism rs7848647

Diverticular disease is a common gastrointestinal disorder seen in over half of all United States adults over the age of sixty years, with approximately 5 percent of the population requiring surgery. According to Walter Koltun, M.D., F.A.C.S, F.A.S.C.R.S., chief, division of colon and rectal surgery at Penn State Hershey Medical Center, “We’re beginning to understand that diverticulitis is caused by a mix of genetic and environmental factors. A strong genetic component for diverticular disease was demonstrated in twin studies done in Europe, showing that about 50 percent of diverticular disease susceptibility is genetically based. We also know genetic influence is complex, and related to multiple genes.” The overall mix of genetic and environmental factors associated with the development of diverticular disease helps to explain the wide phenotypic variation physicians observe clinically, ranging from asymptomatic to life-threatening.

Surgical DiverticulitisThe familial nature of severe diverticulitis has become especially evident based on data gathered through Penn State Hershey’s Colorectal Disease Biobank, established in 1998. “The Biobank provides access to patient records, tissue samples and DNA, allowing us to look at large groups of patients with diverticulitis, including multiple generations of patients in single families with clinical clusters of disease,” says Koltun. The group’s research, recently published in the Annals of Surgery1, demonstrates a significant association between single nuclear polymorphisms (SNPs) in the tumor necrosis factor super family 15 (TFNSF15) gene and the development of diverticulitis requiring surgery.

“The findings tell a unique and compelling story and I think represent a true paradigm shift in our understanding of diverticulitis. We found that mutations in the TNFSF15 gene were associated with diverticulitis requiring surgery,” notes Koltun. TNFSF15 is a gene that codes for a T-cell chemokine involved in T–cell maturation, impacting the ability of the body to regulate immune responses to infection and inflammation. “Such research targets the goal of genetically screening patients with diverticulitis; if for example, they have this polymorphism linked to a more aggressive disease, physicians might choose to perform surgery before the disease causes life-threatening complications [like perforation],” explains Koltun.

Although research is needed before a screening test would become available for broad use, Koltun hopes the new findings will bring more focus on the genetic component. “As we’ve seen with inflammatory bowel disease, the study of the genetic component of diverticulitis can help to identify mechanisms of the disease that haven’t yet been uncovered and identify new therapeutic targets. In the nearer term, genetic research may also change the way patients are screened and treated, with the goal of identifying and more aggressively treating high-risk patients.”



Walter Koltun, M.D.Walter A. Koltun, M.D., F.A.C.S., F.A.S.C.R.S.
Chief, Division of Colon and Rectal Surgery
Peter and Marshia Carlino Chair in Inflammatory Bowel Disease
Professor of Surgery, Penn State College of Medicine
Phone: 717-531-8887
Fellowships: General Surgery, Harvard Medical School; Lahey Hospital & Medical Center
Residency: Brigham & Women’s Hospital
Medical School: Harvard Medical School

1. Connelly TM, Berg AS, Hegarty JP., et al. The TNFSF15 gene single nucleotide polymorphism rs784647 is associated with surgical diverticulitis. Annals of Surgery 2014; 259:1132-1137.

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