<i>FCGR</i>3<i>A</i>基因多态性与溃疡性结肠炎发病风险的相关性分析

林李淼; 袁子蕙; 王伟中; 邵晓晓; 徐缘; 曹曙光; 蒋益

doi:10.16766/j.cnki.issn.1674-4152.004405

FCGR3A基因多态性与溃疡性结肠炎发病风险的相关性分析

doi: 10.16766/j.cnki.issn.1674-4152.004405

1.
温州医科大学附属第二医院消化内科, 浙江温州 325000
2.
温州医科大学第二临床医学院, 浙江温州 325035

基金项目:

浙江省自然科学基金项目 LY23H030004

浙江省中医药科技计划项目 2024ZL616

温州市科技计划项目 Y20240212

详细信息

通讯作者:
蒋益，E-mail：wzjiangyi@yeah.net

中图分类号: R574.62
计量
- 文章访问数: 17
- HTML全文浏览量: 8
- PDF下载量: 2
- 被引次数: 0
出版历程
- 收稿日期: 2025-04-25
- 网络出版日期: 2026-06-02

Associations of FCGR3A gene polymorphisms with the risk of ulcerative colitis

1.
Department of Gastroenterology, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China

摘要

摘要: 目的研究FCGR3A基因多态性与溃疡性结肠炎(UC)发病风险、疾病部位及疾病活动度的关联。方法回顾性纳入2012年1月—2021年1月温州医科大学附属第二医院确诊的545例UC病例及545名性别、年龄相匹配的正常对照者。采用改良Mayo评分评估UC疾病活动度。采用基质辅助激光解吸电离-飞行时间质谱技术检测2组受试者FCGR3A(rs396991, rs4656317)的基因型。使用Haploview 4.2软件评估FCGR3A基因多态性的连锁不平衡模式并构建单倍型。通过logistic回归模型比较2组间基因型分布的差异，并探讨其与疾病临床特征的相关性。结果基因型分析结果表明，UC患者rs396991位点C等位基因频率显著高于健康对照组(P=0.025)，rs4656317位点C等位基因及携带者频率同样明显升高(均P < 0.001)。中重度活动期UC患者rs396991变异等位基因与基因型频率均高于轻度活动期患者(P=0.012、P=0.032)。FCGR3A基因rs4656317与rs396991位点呈高度连锁不平衡(D'=0.920，r²=0.667)。单倍型分析显示，UC组AG(P=0.003)、CG(P=0.006)单倍型频率降低，CC(P=0.002)、AC(P=0.005)单倍型频率升高；且中重度活动期患者AG单倍型降低、CC单倍型升高(P=0.032、P=0.003)。结论 FCGR3A基因的rs396991和rs4656317位点多态性可能与UC易感性相关。rs396991变异还显示出与疾病活动程度的显著关联。
- 溃疡性结肠炎 /
- FCGR3A基因 /
- 多态性 /
- 单核苷酸 /
- 发病风险 /
- 相关性
Abstract: Objective To investigate the association between FCGR3A gene polymorphisms and the risk of ulcerative colitis (UC), disease location, and clinicopathological features related to disease activity. Methods From January 2012 to January 2021, 545 UC patients and 545 age- and gender-matched healthy controls were recruited from the Department of Gastroenterology, the Second Affiliated Hospital of Wenzhou Medical University. The modified Mayo score was employed to assess the disease activity of UC. The FCGR3A polymorphisms (rs396991 and rs4656317) were genotyped using MALDI-TOF mass spectrometry. Haplotype analysis and linkage disequilibrium assessment were performed with Haploview 4.2 software. Results Genotype analysis revealed that the frequency of the C allele at rs396991 was significantly higher in UC patients than in healthy controls (P=0.025), and the frequencies of the C allele and its carriers at rs4656317 were also markedly elevated (both P < 0.001). The frequencies of the variant allele and genotype of rs396991 in patients with moderate-to-severe active UC were both higher than those in patients with mild active UC (P=0.012 and P=0.032, respectively). The rs4656317 and rs396991 loci of theFCGR3A gene exhibited strong linkage disequilibrium (D'=0.920, r²=0.667). Haplotype analysis demonstrated that the frequencies of AG (P=0.003) and CG (P=0.006) haplotypes were decreased, while those of CC (P=0.002) and AC (P=0.005) haplotypes were increased in the UC group; furthermore, the AG haplotype was downregulated and the CC haplotype was upregulated in moderate-to-severe active UC patients (P=0.032 and 0.003, respectively). Conclusion FCGR3A (rs396991, rs4656317) gene variations may be risk factors for UC. In addition, FCGR3A (rs396991) gene variation may also be related to the increased disease activity in UC patients.
- Ulcerative colitis /
- FCGR3A gene /
- Polymorphism /
- Single nucleotide /
- Disease risk /
- Correlation

HTML全文

图 1 FCGR3A基因连锁不平衡结构图

Figure 1. Structure of FCGR3A gene linkage disequilibrium

下载: 全尺寸图片幻灯片

表 1 UC组和HC组间一般临床资料比较

Table 1. Comparison of general clinical data between UC group and HC group

项目	UC组 (n=545)	IFX治疗组 (n=44)	HC组 (n=545)	统计量^a	P值^a
性别(例)				0.093^b	0.760
女性	240	24	235
男性	305	20	310
年龄(x±s，岁)	43.54±9.73	43.00±9.11	44.07±11.56	0.819^c	0.411
吸烟史[例(%)]
吸烟或戒烟不足5年	72(13.2)	7(15.9)	90(16.5)	2.349^b	0.125
从未吸烟者	473(86.8)	37(84.1)	455(83.5)
疾病范围[例(%)]
直肠(E1)	148(27.2)	10(22.7)
左半结肠(E2)	174(31.9)	15(34.1)
广泛结肠(E3)	223(40.9)	19(43.2)
疾病活动度[例(%)]
轻度	213(39.1)	0
中度	284(52.1)	36(81.8)
重度	48(8.8)	8(18.2)
治疗史[例(%)]
5-氨基水杨酸	431(79.1)
糖皮质激素	193(35.4)
免疫抑制剂	52(9.5)
英夫利昔单抗	44(8.1)
维得利珠单抗	9(1.7)
结肠切除术	3(0.6)
注：^a为UC组与HC组比较；^b为χ²值，^c为t值。

下载: 导出CSV

表 2 UC组和HC组之间FCGR3A基因多态性分布比较[频数(%)]

Table 2. Comparison of FCGR3A gene polymorphisms between UC group and HC group [frequency (%)]

FCGR3A基因	UC组 (n=545)	HC组 (n=545)	P值	OR(95% CI)
rs396991
AA	215(39.4)	243(44.6)
AC	260(47.7)	255(46.8)
CC	70(12.9)	47(8.6)
AC+CC	330(60.6)	302(55.4)	0.086	1.235(0.965~1.570)
等位基因A	690(63.3)	741(68.0)
等位基因C	400(36.7)	349(32.0)	0.025	1.227(1.027~1.464)
rs4656317
GG	170(31.2)	227(41.7)
GC	288(52.8)	264(48.4)
CC	87(16.0)	54(9.9)
GC+CC	375(68.8)	318(58.3)	< 0.001	1.575(1.227~2.020)
等位基因G	628(57.6)	718(65.9)
等位基因C	462(42.4)	372(34.1)	< 0.001	1.420(1.194~1.690)

下载: 导出CSV

表 3 FCGR3A基因多态性与UC疾病活动度的关系[频数(%)]

Table 3. Relationship between FCGR3A gene polymorphisms and disease activity in UC [frequency (%)]

FCGR3A基因	轻度 (n=213)	中度+重度 (n=332)	P值	OR(95% CI)
rs396991
AA	96(45.1)	119(35.8)
AC	97(45.5)	163(49.1)
CC	20(9.4)	50(15.1)
AC+CC	117(55.9)	213(64.2)	0.032	1.471(1.034~2.092)
等位基因A	289(67.8)	401(60.4)
等位基因C	137(32.2)	263(39.6)	0.012	1.394(1.079~1.805)
rs4656317
GG	72(33.8)	98(29.5)
GC	116(54.5)	172(51.8)
CC	25(11.7)	62(18.7)
GC+CC	141(66.2)	234(70.5)	0.261	1.243(0.853~1.791)
等位基因G	260(61.0)	368(55.4)
等位基因C	166(39.0)	296(44.6)	0.060	1.271(0.993~1.634)

下载: 导出CSV

参考文献(24)

[1]	崔晓婷, 芦杰, 牛昊书, 等. 溃疡性结肠炎患者病情发展中ERK1/2信号通路变化及其与肠道机会性感染的关联[J]. 中华全科医学, 2024, 22(10): 1636-1639. doi: 10.16766/j.cnki.issn.1674-4152.003700 CUI X T, LU J, NIU H S, et al. Changes in ERK1/2 signaling pathway in the progression of ulcerative colitis and its association with intestinal opportunistic infections[J]. Chinese Journal of General Practice, 2024, 22(10): 1636-1639. doi: 10.16766/j.cnki.issn.1674-4152.003700
[2]	ABDEL-WAHED M A, SABBOUR G S, HAMED A I, et al. FCGR3A V158F gene polymorphism and trastuzumab response in HER2-positive breast cancer patients[J]. Sci Rep, 2024, 14(1): 26037. DOI: 10.1038/s41598-024-76024-6.
[3]	XUE D, TABIB T, MORSE C, et al. Expansion of Fcγ Receptor Ⅲa-positive macrophages, ficolin 1-positive monocyte-derived dendritic cells, and plasmacytoid dendritic cells associated with severe skin disease in systemic sclerosis[J]. Arthritis Rheumatol, 2022, 74(2): 329-341. doi: 10.1002/art.41813
[4]	MUSOLINO A, GRADISHAR W J, RUGO H S, et al. Role of Fcγ receptors in HER2-targeted breast cancer therapy[J]. J Immunother Cancer, 2022, 10(1): e003171. DOI: 10.1136/jitc-2021-003171.
[5]	HAYAT S, BABU G, DAS A, et al. Fc-gamma Ⅲa-V158F receptor polymorphism contributes to the severity of Guillain-Barre syndrome[J]. Ann Clin Transl Neurol, 2020, 7(6): 1040-1049. doi: 10.1002/acn3.51072
[6]	ANDREEVA I, KOLB P, RODON L, et al. Fcγ-receptor-IIIA bioactivity of circulating and synovial immune complexes in rheumatoid arthritis[J]. RMD Open, 2024, 10(3): e004190. DOI: 10.1136/rmdopen-2024-004190.
[7]	ROBINSON J I, MD YUSOF M Y, DAVIES V, et al. Comprehensive genetic and functional analyses of Fc gamma receptors influence on response to rituximab therapy for autoimmunity[J]. EBioMedicine, 2022, 86: 104343. DOI: 10.1016/j.ebiom.2022.104343.
[8]	CHEN H Z, MAUL-PAVICIC A, HOLZER M, et al. Detection and functional resolution of soluble immune complexes by an FcγR reporter cell panel[J]. EMBO Mol Med, 2022, 14(1): e14182. DOI: 10.15252/emmm.202114182.
[9]	CAI D X, HU W T, CAI Y L, et al. Integrated analysis of ferroptosis and immune infiltration in ulcerative colitis based on bioinformatics[J]. J Inflamm Res, 2025, 18: 3535-3549. doi: 10.2147/JIR.S501651
[10]	STEERE B, SCHMITZ J, POWELL N, et al. Mirikizumab regulates genes involved in ulcerative colitis disease activity and anti-TNF resistance: results from a phase 2 study[J]. Clin Transl Gastroenterol, 2023, 14(7): e00578. DOI: 10.14309/ctg.0000000000000578.
[11]	杨红, 钱家鸣. 《中国溃疡性结肠炎诊治指南(2023年·西安)》解读[J]. 北京医学, 2024, 46(11): 999-1002. YANG H, QIAN J M. Interpretation of Chinese guidelines for the diagnosis and treatment of ulcerative colitis (2023· Xi'an)[J]. Beijing Medical Journal, 2024, 46(11): 999-1002.
[12]	DÉMARIS A, WIDIGSON E S K, ILVEMARK J, et al. Ulcerative colitis and acute severe ulcerative colitis patients are overlooked in infliximab population pharmacokinetic models: results from a comprehensive review[J]. Pharmaceutics, 2022, 14(10): 2095. DOI: 10.3390/pharmaceutics14102095.
[13]	KAMAL M E, WERIDA R H, RADWAN M A, et al. Efficacy and safety of infliximab and adalimumab in inflammatory bowel disease patients[J]. Inflammopharmacology, 2024, 32(5): 3259-3269. doi: 10.1007/s10787-024-01508-w
[14]	ADAMS S M, CLOSE E D, SHREENATH A P. Ulcerative colitis: rapid evidence review[J]. Am Fam Physician, 2022, 105(4): 406-411.
[15]	DAMELANG T, BRINKHAUS M, VAN OSCH T L J, et al. Impact of structural modifications of IgG antibodies on effector functions[J]. Front Immunol, 2023, 14: 1304365. DOI: 10.3389/fimmu.2023.1304365.
[16]	MILLS K H G. IL-17 and IL-17-producing cells in protection versus pathology[J]. Nat Rev Immunol, 2023, 23(1): 38-54.
[17]	PORTER R J, KALLA R, HO G T. Ulcerative colitis: recent advances in the understanding of disease pathogenesis[J]. F1000Res, 2020, 9: F1000 Faculty Rev-294. DOI: 10.12688/f1000research.20805.1.
[18]	AL-SOFI R F, BERGMANN M S, NIELSEN C H, et al. The association between genetics and response to treatment with biologics in patients with psoriasis, psoriatic arthritis, rheumatoid arthritis, and inflammatory bowel diseases: a systematic review and meta-analysis[J]. Int J Mol Sci, 2024, 25(11): 5793. DOI: 10.3390/ijms25115793.
[19]	李霞, 王磊, 颜登国. FcγRⅢa最新研究进展[J]. 中国肿瘤临床与康复, 2021, 28(2): 253-256. LI X, WANG L, YAN D G. The latest research progress of FcγRⅢa[J]. Chinese Journal of Clinical Oncology and Rehabilitation, 2021, 28(2): 253-256.
[20]	BIAŁY S, IWASZKO M, ŚWIERKOT J, et al. Genetic variability of three common NK and γδ T cell receptor genes (FCγ3R, NCR3, and DNAM-1) and their role in Polish patients with rheumatoid arthritis and ankylosing spondylitis[J]. Immunol Res, 2024, 72(4): 614-625. doi: 10.1007/s12026-024-09488-3
[21]	ZHU K Z, DING X L, CHEN Z Y, et al. Association between genetic variants and development of antibodies to infliximab: a cross-sectional study in Chinese patients with Crohn's disease[J]. Front Pharmacol, 2023, 14: 1096816. DOI: 10.3389/fphar.2023.1096816.
[22]	GUGA S, WANG Y X, GRAHAM D C, et al. A review of genetic risk in systemic lupus erythematosus[J]. Expert Rev Clin Immunol, 2023, 19(10): 1247-1258. doi: 10.1080/1744666X.2023.2240959
[23]	ROY-CHOWDHURY E, BRAUNS N, HELMKE A, et al. Human CD16⁺ monocytes promote a pro-atherosclerotic endothelial cell phenotype via CX3CR1-CX3CL1 interaction[J]. Cardiovasc Res, 2021, 117(6): 1510-1522.
[24]	LU C H, LI K J, WU C H, et al. The FcγRIII engagement augments PMA-stimulated neutrophil extracellular traps (NETs) formation by granulocytes partially via cross-talk between Syk-ERK-NF-κB and PKC-ROS signaling pathways[J]. Biomedicines, 2021, 9(9): 1127. DOI: 10.3390/biomedicines9091127.