Background: Colonic diverticulosis is a common condition, particularly in the elderly population. While dietary habits, obesity, smoking, and physical inactivity contribute to its pathogenesis, emerging evidence highlights a genetic predisposition affecting extracellular matrix (ECM) remodeling, inflammation, and connective tissue integrity. The aim
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Background: Colonic diverticulosis is a common condition, particularly in the elderly population. While dietary habits, obesity, smoking, and physical inactivity contribute to its pathogenesis, emerging evidence highlights a genetic predisposition affecting extracellular matrix (ECM) remodeling, inflammation, and connective tissue integrity. The aim of this systematic review was to summarize genetic determinants of colonic diverticulosis.
Methods: The PubMed
® database was searched for original studies in humans. The inclusion criteria were named genetic factor and confirmed diverticulosis. Patients with diverticulitis and diverticular diseases were excluded from this review.
Results: Out of 137 publications, 10 articles met the inclusion criteria: six large association studies (GWAS) and four cross-sectional studies. The genes regulating ECM turnover, including
TIMP1,
MMP3, and
MMP9, are involved in diverticulosis development. The
TIMP1 (
rs4898) T allele has been associated with increased susceptibility, potentially due to its role in ECM remodeling. Similarly,
MMP3 (
rs3025058) and
MMP9 (
rs3918242) polymorphisms contribute to altered collagen degradation. The
COL3A1 (
rs3134646) variant coding modified collagen type III may promote diverticular formation. Other genes, such as
ARHGAP15 (
rs4662344,
rs6736741), affect cytoskeletal dynamics. Identified in GWAS studies, gene candidates may be grouped into blood group and immune system-related genes (
ABO,
HLA-DQA1,
HLA-H,
OAS1,
TNFSF13,
FADD), extracellular matrix and connective tissue genes (
COL6A1,
COLQ,
EFEMP1,
ELN,
HAS2,
TIMP2), signaling and cell communication (
BMPR1B,
WNT4,
RHOU,
PHGR1,
PCSK5), nervous system and neurodevelopment (
BDNF,
CACNB2,
GPR158,
SIRT1,
SCAPER,
TRPS1), metabolism and transporters (
SLC25A28,
SLC35F3,
RBKS,
PPP1R14A,
PPP1R16B), lipids and cholesterol (
LDAH,
LYPLAL1,
STARD13), transcription and gene regulation (
ZBTB4,
UBTF,
TNRC6B), apoptosis (
FADD,
PIAS1), and poorly characterized genes (
C1TNF7,
ENSG00000224849,
ENSG00000251283,
LINC01082,
DISP2,
SNX24,
THEM4,
UBL4B,
UNC50,
WDR70,
SREK1IP1).
Conclusions: There are a number of gene variants that probably predispose to colonic diverticulosis. Detailed characterization of the multigene background of diverticulosis will enable appropriate therapeutic or preventive interventions in the future.
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