From polymorphism to phenotype: FADS2 rs174538, fatty acid signatures and disease activity in Japanese Crohn’s disease

Table 1 Representative studies of FADS-related genetic variants and loci in inflammatory bowel disease

FADS-related variant /Locus	Disease context	Population /design	FADS-related finding	Ref.
FADS2 rs2277284	CD	Japanese case-control genetic study, 52 patients compared with Japanese reference data	The allele frequency of FADS2 rs2277284 was significantly higher in patients with CD than in controls, with an OR of 4.4	[13]
FADS1 rs174561, rs174556; FADS2 rs3834458, rs174575	CD and UC	Nested case-control study within NHS and NHS II, including 101 CD cases, 139 UC cases, and 495 controls	No clear independent association between FADS polymorphisms and CD or UC risk was observed. The diet-related association was more strongly modified by other lipid metabolism genes than by FADS	[14]
FADS1 rs174547, rs174575; FADS2 rs11230815, rs17831757, rs968567, rs174627	CD	Pediatric case-control study, 182 CD cases and 250 controls	FADS1 rs174547 and rs174575 showed no significant association with CD risk. For FADS2, rs11230815, rs17831757, rs968567, and rs174627 each exhibited an interaction with a high ω6/ω3 dietary ratio; only carriers of these specific genotypes had a significantly increased CD risk when consuming a high ratio. Notably, rs17831757 itself was not independently associated with CD	[15]
rs174537 (near FADS1); FADS2 rs174538; chr11 FADS1-FADS2-TMEM258 locus	IBD	Human eQTL fine-mapping and mechanistic study in cells, mouse DSS colitis, and colonic organoids	rs968567 is associated with rheumatoid arthritis and lipid metabolism, while IBD risk is associated with rs174537 in the same region (which is associated with increased TMEM258 expression)	[16]
rs174537 (near FADS1)	CD and UC	Large GWAS meta-analysis and validation study	In intestinal tissue eQTL analysis, the expression of the known risk site rs174537 for IBD was significantly correlated with that of FADS2	[17]

IBD: Inflammatory bowel disease; CD: Crohn’s disease; UC: Ulcerative colitis; NHS: Nurses’ Health Study; GWAS: Genome-wide association study; OR: Odds ratio.