# Mendelian Randomization Reveals Genetic Associations Between Immune Traits and Urethral Stricture

**Authors:** Qiang Guo, Jin-Cheng Guo, Zhan-Long Zheng, Ke Yang, Jing-Qi Wang, Cheng-Yong Li, Yu-Jia Xi

PMC · DOI: 10.1155/mi/3748167 · Mediators of Inflammation · 2026-02-27

## TL;DR

This study uses genetic data to find a potential link between immune cell traits and urethral stricture, suggesting a possible role for immune cells in its development.

## Contribution

The study identifies 37 immune phenotypes with causal links to urethral stricture using Mendelian randomization.

## Key findings

- 37 immune phenotypes showed suggestive causal relationships with urethral stricture.
- Sensitivity analyses confirmed no heterogeneity or pleiotropy in the results.
- The findings include 13 B cell subtypes and other immune cell types linked to the condition.

## Abstract

There is currently little research on the association between immune traits and urethral stricture, and the diversity of immune cell subtypes leads to an unclear association with urethral stricture. This study investigated the relationship between immune cells and urethral stricture using the Mendelian randomization (MR) technique.

We assessed the causative relationships between urethral stricture (N = 341,285) and 731 immunological characteristics (N = 3757). The main technique was the inverse‐variance weighted (IVW) approach, which was supplemented by MR‐Egger and weighted median (WM). The robustness of MR results was assessed using sensitivity analyses, primarily the Egger intercept, Cochran’s Q test, MR‐PRESSO, and leave‐one‐out test.

Our findings revealed that 37 immune phenotypes have suggestive causal relationships with urethral stricture, including 13 subtypes of B cells, four classical dendritic cells, three myeloid cells, five monocytes, four TBNK, five Treg cells, and three maturation stages of T cells. Sensitivity analyses revealed neither heterogeneity nor pleiotropy.

Our findings supported a potential causal relationship between immune cells and urethral stricture. This may guide the management and treatment of urethral stricture in the future.

## Linked entities

- **Diseases:** urethral stricture (MONDO:0002127)

## Full-text entities

- **Genes:** TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, CD38 (CD38 molecule) [NCBI Gene 952] {aka ADPRC 1, ADPRC1, cADPR1}, CD28 (CD28 molecule) [NCBI Gene 940] {aka IMD123, Tp44}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, IL17A (interleukin 17A) [NCBI Gene 3605] {aka CTLA-8, CTLA8, IL-17, IL-17A, IL17, ILA17}, Serpine1 (serine (or cysteine) peptidase inhibitor, clade E, member 1) [NCBI Gene 18787] {aka PAI-1, PAI1, Planh1}, CD86 (CD86 molecule) [NCBI Gene 942] {aka B7-2, B7.2, B70, BU63, CD28LG2, CD86 v6}, CCL28 (C-C motif chemokine ligand 28) [NCBI Gene 56477] {aka CCK1, MEC, SCYA28}, CCR7 (C-C motif chemokine receptor 7) [NCBI Gene 1236] {aka BLR2, CC-CKR-7, CCR-7, CD197, CDw197, CMKBR7}, NLRP3 (NLR family pyrin domain containing 3) [NCBI Gene 114548] {aka AGTAVPRL, AII, AVP, C1orf7, CIAS1, CLR1.1}, PTPRC (protein tyrosine phosphatase receptor type C) [NCBI Gene 5788] {aka B220, CD45, CD45R, GP180, IMD105, L-CA}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, CD24 (CD24 molecule) [NCBI Gene 100133941] {aka CD24A}, Ccl2 (C-C motif chemokine ligand 2) [NCBI Gene 20296] {aka HC11, JE, MCAF, MCP-1, MCP1, SMC-CF}, ENTPD1 (ectonucleoside triphosphate diphosphohydrolase 1) [NCBI Gene 953] {aka ATP-DPH, ATPDase, CD39, NTPDase-1, SPG64}, IL2RA (interleukin 2 receptor subunit alpha) [NCBI Gene 3559] {aka CD25, IDDM10, IL2R, IMD41, TCGFR, p55}, Ly6c1 (lymphocyte antigen 6 family member C1) [NCBI Gene 17067] {aka Ly-6C, Ly-6C1, Ly6c}, IL7R (interleukin 7 receptor) [NCBI Gene 3575] {aka CD127, CDW127, IL-7R-alpha, IL-7Ralpha, IL7RA, IL7Ralpha}, CD33 (CD33 molecule) [NCBI Gene 945] {aka CD33rSiglec, SIGLEC-3, SIGLEC3, p67}, TNFRSF1A (TNF receptor superfamily member 1A) [NCBI Gene 7132] {aka CD120a, FPF, TBP1, TNF-R, TNF-R-I, TNF-R55}, CD27 (CD27 molecule) [NCBI Gene 939] {aka S152, S152. LPFS2, T14, TNFRSF7, Tp55}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, Fcgr3 (Fc receptor, IgG, low affinity III) [NCBI Gene 14131] {aka CD16}, Cd14 (CD14 antigen) [NCBI Gene 12475], SELL (selectin L) [NCBI Gene 6402] {aka CD62L, LAM1, LECAM1, LEU8, LNHR, LSEL}, ITGAM (integrin subunit alpha M) [NCBI Gene 3684] {aka CD11B, CR3A, HNA-4, MAC-1, MAC1A, MO1A}
- **Diseases:** infectious urethritis (MESH:D014526), infection (MESH:D007239), MR (MESH:C562757), liver fibrosis (MESH:D008103), fibrosis (MESH:D005355), thrombosis (MESH:D013927), inflammation (MESH:D007249), Urethral Stricture (MESH:D014525), obstruction of the urethra (MESH:D014523), lichen sclerosis (MESH:D018459), type II AEC damage (MESH:C535847)
- **Chemicals:** vitamin D (MESH:D014807), HVEM (-), DNTs (MESH:C023514)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** H17 — Mus musculus (Mouse), Hybridoma (CVCL_B0EE)

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12949340/full.md

## References

66 references — full list in the complete paper: https://tomesphere.com/paper/PMC12949340/full.md

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Source: https://tomesphere.com/paper/PMC12949340