性激素与口腔扁平苔藓间的因果关系

doi:10.13591/j.cnki.kqyx.2026.08.002

摘要/Abstract

摘要：

目的采用孟德尔随机化方法(Mendelian randomization,MR)探究血清性激素水平与口腔扁平苔藓(oral lichen planus,OLP)的因果关系,并进行初步生物学验证。方法利用总睾酮(total testosterone, TT)、生物可利用睾酮(bioavailable testosterone, BT)、雌二醇(estradiol, E2)、性激素结合球蛋白(sex hormone-binding globulin, SHBG)和脱氢表雄酮硫酸盐(dehydroepiandrosterone sulfate, DHEAs)的公开全基因组关联研究(GWAS)数据及芬兰FinnGen数据库中的OLP数据,进行双向两样本MR分析,以逆方差加权法(IVW)为主评估性激素与OLP的因果关系,并通过敏感性分析评估结果稳健性,同时采用SHBG血清分析加以验证。结果男性血清SHBG水平升高增加OLP发生风险(OR=1.26,P=0.04),而女性中无此关联。无论男女,TT、BT、E2、DHEAs水平与OLP无显著因果关联(P>0.05)。反向MR未发现OLP对上述血清性激素水平的因果影响。敏感性分析支持结果的稳定性。男性SHBG血清学验证结果在趋势上支持MR分析发现,但年龄调整后差异减弱。结论血清SHBG水平升高增加男性OLP的发生风险,而TT、BT、E2、DHEAs水平与OLP无因果关联。

关键词: 孟德尔随机化, 口腔扁平苔藓, 性激素, 性激素结合球蛋白

Abstract:

Objective To investigate the causal relationship between serum sex hormone levels and oral lichen planus (OLP) using Mendelian randomization (MR), with supplementary serological validation. Methods A bidirectional two-sample MR analysis was conducted using publicly available genome-wide association study(GWAS) summary statistics for total testosterone (TT), bioavailable testosterone (BT), estradiol (E2), sex hormone-binding globulin (SHBG), and dehydroepiandrosterone sulfate (DHEAs), alongside OLP data from the FinnGen database. The inverse variance weighted (IVW) method served as the primary analytical approach, supported by sensitivity analyses, while serum SHBG analysis was conducted for verification. Results Genetically predicted higher serum SHBG levels were associated with an increased risk of OLP in males (OR=1.26, P=0.04), but not in females. No causal effects were observed between TT, BT, E2, or DHEAs and OLP in either gender (P>0.05). Reverse MR analyses showed no causal effect of OLP on serum sex hormone levels. Sensitivity analyses supported the stability of these findings. Serological analyses in males showed trends consistent with the MR results, although the differences were attenuated after age adjustment. Conclusion Elevated serum SHBG levels are causally linked to an increased risk of OLP in males, while no significant causal associations are found for TT, BT, E2, or DHEAs.

Key words: Mendelian randomization, oral lichen planus, sex hormone, sex hormone-binding globulin

中图分类号:

R778.1

孙昕奕, 熊美珍, 唐一明, 王锋, 陈伟, 李芷. 性激素与口腔扁平苔藓间的因果关系[J]. 口腔医学, 2026, 46(8): 567-573.

SUN Xinyi, XIONG Meizhen, TANG Yiming, WANG Feng, CHEN Wei, LI Zhi. Causal relationship between sex hormones and oral lichen planus[J]. Stomatology, 2026, 46(8): 567-573.

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参考文献 34

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暴露因素	年份	人群	样本量	SNP	网络来源
TT-M	2020	欧洲人群	199 569	12 321 875	https://opengwas.io/datasets/ieu-b-4865
TT-F	2020	欧洲人群	199 569	12 321 875	https://opengwas.io/datasets/ieu-b-4864
BT-M	2020	欧洲人群	184 205	12 321 875	https://opengwas.io/datasets/ieu-b-4868
BT-F	2020	欧洲人群	180 386	12 321 875	https://opengwas.io/datasets/ieu-b-4869
E2-M	2021	欧洲人群	147 690	7 489 424	https://opengwas.io/datasets/ebi-a-GCST90020091
E2-F	2021	欧洲人群	163 985	7 488 193	https://opengwas.io/datasets/ebi-a-GCST90020092
SHBG-M	2020	欧洲人群	185 221	12 321 875	https://opengwas.io/datasets/ieu-b-4871
SHBG-F	2020	欧洲人群	214 989	12 321 875	https://opengwas.io/datasets/ieu-b-4870
DHEAs	2017	欧洲人群	9 722	21 770 677	https://opengwas.io/datasets/ebi-a-GCST004941

暴露	结局	nSNP	逆方差加权法		MR-Egger回归法		加权中位数法		简单众数法		加权众数法
暴露	结局	nSNP	P	OR	P	OR	P	OR	P	OR	P	OR
TT-M	OLP	146	0.44	1.11	0.84	0.95	0.90	1.03	0.69	1.20	0.99	1.00
TT-F	OLP	98	0.80	0.95	0.83	1.08	0.58	1.20	0.52	0.66	0.94	1.03
BT-M	OLP	69	0.78	0.94	0.34	0.64	0.99	1.00	0.37	1.81	0.63	0.82
BT-F	OLP	116	0.41	0.86	0.74	0.89	0.42	1.26	0.39	0.60	0.52	1.21
E2-M	OLP	11	0.59	1.08	0.49	0.74	0.69	1.07	0.50	1.19	0.65	1.10
E2-F	OLP	19	0.76	1.08	0.66	1.26	0.24	1.38	0.64	0.79	0.37	1.39
SHBG-M	OLP	186	0.04	1.26	0.99	1.00	0.34	1.19	0.28	1.49	0.25	1.26
SHBG-F	OLP	178	0.07	1.26	0.69	1.09	0.94	0.98	0.84	0.91	0.73	1.09
DHEAs	OLP	6	0.30	1.29	0.55	1.27	0.34	1.30	0.17	2.27	0.57	1.19

暴露	结局	nSNP	逆方差加权法		MR-Egger回归法		加权中位数法		简单众数法		加权众数法
暴露	结局	nSNP	P	OR	P	OR	P	OR	P	OR	P	OR
OLP	TT-M	4	0.71	1.00	0.79	1.03	0.84	1.00	0.64	1.01	0.43	1.01
OLP	TT-F	4	0.60	1.00	0.57	0.98	0.76	1.00	0.98	1.00	0.74	1.00
OLP	BT-M	4	0.98	1.00	0.23	0.94	0.79	1.00	0.67	1.01	0.59	1.01
OLP	BT-F	4	0.70	1.00	0.63	0.96	0.63	1.00	0.32	1.02	0.40	1.02
OLP	E2-M	3	0.35	0.97	0.40	0.83	0.41	0.97	0.59	0.97	0.44	0.95
OLP	E2-F	3	0.32	1.03	0.54	0.89	0.27	1.04	0.34	1.06	0.34	1.06
OLP	SHBG-M	4	0.81	0.99	0.47	1.13	0.23	0.99	0.34	0.98	0.24	0.98
OLP	SHBG-F	4	0.64	0.99	0.68	1.05	0.35	0.99	0.34	0.97	0.60	1.01
OLP	DHEAs	5	0.18	0.97	0.62	1.05	0.21	0.97	0.17	0.94	0.30	0.97

暴露	结局	异质性检验				MR-Egger截距检验
暴露	结局	方法	Q	自由度	P	截距	标准误	P
TT-M	OLP	IVW	143.627	145	0.517	0.007	0.009	0.443
TT-F	OLP	IVW	116.854	97	0.083	-0.005	0.012	0.676
BT-M	OLP	IVW	74.058	68	0.287	0.015	0.016	0.350
BT-F	OLP	IVW	130.689	115	0.150	-0.001	0.013	0.936
E2-M	OLP	IVW	7.601	10	0.668	0.061	0.064	0.368
E2-F	OLP	IVW	28.569	18	0.054	-0.017	0.049	0.729
SHBG-M	OLP	IVW	183.172	185	0.524	0.011	0.008	0.170
SHBG-F	OLP	IVW	165.081	177	0.730	0.006	0.008	0.447
DHEAs	OLP	IVW	3.388	5	0.640	0.003	0.038	0.945
OLP	TT-M	IVW	11.553	3	0.009	-0.009	0.025	0.748
OLP	TT-F	IVW	2.249	3	0.522	0.006	0.011	0.615
OLP	BT-M	IVW	3.559	3	0.313	0.020	0.011	0.222
OLP	BT-F	IVW	10.832	3	0.013	0.015	0.024	0.591
OLP	E2-M	IVW	1.936	2	0.380	0.046	0.039	0.448
OLP	E2-F	IVW	1.291	2	0.525	0.041	0.036	0.460
OLP	SHBG-M	IVW	39.171	3	<0.001	-0.038	0.041	0.446
OLP	SHBG-F	IVW	20.960	3	<0.001	-0.017	0.031	0.631
OLP	DHEAs	IVW	6.990	4	0.136	-0.025	0.029	0.449

变量	回归系数	95%CI	P
组别(OLP/对照)	9.30	[-9.15,27.76]	0.302
年龄	0.66	[-0.01,1.32]	0.053