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中华临床医师杂志(电子版) ›› 2026, Vol. 20 ›› Issue (04) : 256 -264. doi: 10.3877/cma.j.issn.1674-0785.2026.04.002

临床研究

基于遗传与代谢组学初步分析rs1426371在膝骨关节炎与动脉硬化共患病中的作用
王茂盛1, 康清源2, 肖文韬1, 王海东1, 袁平3, 张克石2, 毛天明4,†(), 关振鹏2,†()   
  1. 1　830054　新疆乌鲁木齐，新疆医科大学第二临床医学院
    2　100144　北京，北京大学首钢医院骨科
    3　100089　北京，航天医疗健康科技集团有限公司科技处
    4　843000　新疆阿克苏，阿克苏地区中医医院保膝外科
  • 收稿日期:2026-02-28 出版日期:2026-04-30
  • 通信作者: 毛天明, 关振鹏
  • 基金资助:
    北京市卫生健康委员会首都卫生发展科研专项(首发2024-2G-6043); 国家重点研究计划(2023YFC3604900)

Role of rs1426371 in the comorbidity of knee osteoarthritis and atherosclerosis: genetic and metabolomic insights

Maosheng Wang1, Qingyuan Kang2, Wentao Xiao1, Haidong Wang1, Ping Yuan3, Keshi Zhang2, Tianming Mao4,†(), Zhenpeng Guan2,†()   

  1. 1 Second Clinical Medical College of Xinjiang Medical University, Urumqi 830054, China
    2 Department of Orthopedics, Peking University Shougang Hospital, Beijing 100144, China
    3 Science and Technology Department, Aerospace Healthcare Technology Group Co., Ltd., Beijing 100089, China
    4 Department of Knee Preservation Surgery, Aksu Prefecture Traditional Chinese Medicine Hospital, Aksu 843000, China
  • Received:2026-02-28 Published:2026-04-30
  • Corresponding author: Tianming Mao, Zhenpeng Guan
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引用本文：

王茂盛, 康清源, 肖文韬, 王海东, 袁平, 张克石, 毛天明, 关振鹏. 基于遗传与代谢组学初步分析rs1426371在膝骨关节炎与动脉硬化共患病中的作用[J/OL]. 中华临床医师杂志(电子版), 2026, 20(04): 256-264.

Maosheng Wang, Qingyuan Kang, Wentao Xiao, Haidong Wang, Ping Yuan, Keshi Zhang, Tianming Mao, Zhenpeng Guan. Role of rs1426371 in the comorbidity of knee osteoarthritis and atherosclerosis: genetic and metabolomic insights[J/OL]. Chinese Journal of Clinicians(Electronic Edition), 2026, 20(04): 256-264.

目的

探讨膝骨关节炎（KOA）与动脉硬化（AS）之间是否存在共享的遗传风险位点及共同的疾病机制。

方法

纳入北京大学首钢医院的33例受试者，分为对照组（n=8）、KOA组（n=11）及KOA-AS组（n=14）。通过文献检索与全基因组关联研究（GWAS）数据筛选候选单核苷酸多态性（SNP），采用MassARRAY质谱技术进行基因分型，并通过FinnGen数据库进行验证。同时，利用靶向代谢组学（UPLC-MS/MS）检测血清代谢物，分析其变化趋势并富集相关通路。

结果

在检测的候选SNP中，位点rs1426371（位于WSCD2基因）在Bonferroni校正后仍显示出KOA与AS组间的显著基因频率差异（P＜0.001）。数据库验证提示该位点与肌肉骨骼疾病及代谢性疾病（如2型糖尿病、高血压）相关。代谢组学分析鉴定出276种代谢物，富集分析发现组氨酸代谢和甘氨酸-丝氨酸-苏氨酸代谢途径在KOA及KOA-AS组中发生显著改变，相关代谢物包括组胺、咪唑乙酸、甘氨酸等。

结论

本研究初步发现rs1426371可能是KOA与AS的共享遗传风险位点，其可能通过影响组氨酸、甘氨酸代谢途径参与两种疾病的共同病理生理过程，为理解其“代谢性炎症”共患病机制提供了遗传与代谢层面的线索。

关键词: 膝骨关节炎, 动脉硬化, 单核苷酸多态性, 共享遗传机制, rs1426371
Objective

To explore whether there are shared genetic risk loci and common disease mechanisms between knee osteoarthritis (KOA) and arteriosclerosis (AS).

Methods

Thirty-three subjects enrolled at Peking University Shougang Hospital were divided into a control group (n=8), a KOA group (n=11), and a KOA-AS group (n=14). Candidate single nucleotide polymorphisms (SNPs) were selected through literature review and genome-wide association study (GWAS) data. Genotyping was performed using MassARRAY mass spectrometry, and the results were validated using the FinnGen database. Additionally, targeted metabolomics (UPLC-MS/MS) was employed to detect serum metabolites, analyze their changing trends, and identify enriched pathways.

Results

Among the candidate SNPs tested, the rs1426371 locus (located within the WSCD2 gene) demonstrated a significant difference in allele frequency between the KOA and AS groups, even after Bonferroni correction (P＜0.001). Database validation indicated that this locus is associated with musculoskeletal and metabolic diseases, including type 2 diabetes and hypertension. Metabolomic analysis identified 276 metabolites. Enrichment analysis revealed significant alterations in histidine metabolism and glycine-serine-threonine metabolism pathways in both the KOA and KOA-AS groups, involving metabolites including histamine, imidazoleacetic acid, and glycine.

Conclusion

This preliminary study suggests that rs1426371 may serve as a shared genetic risk locus for KOA and AS. It potentially contributes to the common pathophysiological processes of both diseases by influencing histidine and glycine metabolic pathways. These findings provide genetic and metabolic insights into the "metabolic inflammation" mechanism underlying KOA-AS comorbidity.

Key words: Knee osteoarthritis, Atherosclerosis, Single nucleotide polymorphism, Shared genetic mechanism, rs1426371
表1 研究对象基本信息及临床指标
临床指标 对照组（n=8） KOA组（n=11） KOA-AS组（n=14） 合计（n=33）
性别[女性，例（%）] 4（50.0） 8（72.73） 11（78.57） 23（66.70）
年龄（岁，
±s）		 52.75±16.96 66.00±7.03 64.64±13.36 62.21±13.44
收缩压（mmHg，
±s）		 122.17±19.05 130.09±9.54 131.29±16.23 129.10±14.74
舒张压（mmHg，
±s）		 73.33±8.91 76.91±5.94 72.71±11.46 74.32±9.26
BMI（kg/m2，
±s）		 25.25±5.56 26.57±2.69 25.62±3.44 25.86±3.63
葡萄糖（mmol/L，
±s）		 6.26±0.99 7.14±1.48 6.50±1.55 6.68±1.44
IL-6（pg/ml，
±s）		 2.43±1.85 8.34±8.25 3.51±2.31 5.14±5.75
血沉（mm/h，
±s）		 7.40±2.20 14.80±14.15 12.25±8.71 12.30±10.45
表2 相关SNP基本信息
rs ID Gene Chr. Position
rs10038860 SPRY4-AS1 5 142430373
rs10831476 MAml2 11 96063746
rs10842226 SOX5 12 23806655
rs10237429 TBXAS1 7 139828797
rs10256282 TBXAS1 7 139828645
rs10843013 - 12 27872263
rs10974438 GLIS3 9 4291928
rs11096957 TLR10 4 38774870
rs10306194 PTGS1 9 122394919
rs11790782 PTGES 9 129744368
rs1149620 TSKU 11 76795528
rs11705555 22 27810924
rs12193102 SUPT3H 6 45177665
rs12075 ACKR1 1 159205564
rs12526453 PHACTR1 6 12927312
rs12775980 SVIL 10 29570927
rs12901372 SMAD3 15 67078168
rs12914479 - 15 98631599
rs1330344 PTGS1 9 122369409
rs1333049 - 9 22125504
rs13107325 SLC39A8 4 102267552
rs1426371 WSCD2 12 108236003
rs143384 GDF5 20 35437976
rs1537373 CDKN2B-AS1 9 22103342
rs1799864 CCR2 3 46357717
rs1517572 - 11 28808335
rs1546737 DNAH1 3 52373025
rs1631174 - 11 47952821
rs1805087 MTR 1 236885200
rs1951276 - 14 35384182
rs17615906 LOC105379168 5 128682720
rs1889570 IL17F 6 52245936
rs1913707 LOC124900668 4 13037816
rs2026458 PHACTR1 6 12825642
rs2066826 PTGS2 1 186676795
rs20417 PACERR 1 186681189
rs2066928 - 5 30843680
rs2163832 SLC44A2 19 10635088
rs2241270 PTGES 9 129752610
rs2664593 ALOX15 17 4641837
rs2273650 NFKBIA 14 35401592
rs2275913 IL17A 6 52186235
rs2605098 LYPLAL1-AS1 1 219470307
rs2665580 SULT2B1 19 48574884
rs2857656 CCL2 17 34254988
rs2622873 COL11A1 1 103000497
rs2791549 LYPLAL1-AS1 1 219484661
rs28411362 LOC105377979 6 121970573
rs2876300 PHACTR1 6 12893871
rs34489123 TFPI2 7 93889174
rs2856821 HLA-DPA1 6 33078965
rs3129900 TSBP1 6 32338202
rs34195470 WWP2 16 69921787
rs3825807 ADAMTS7 15 78796769
rs3842788 PTGS1 9 122377927
rs3755381 TGFA 2 70491563
rs3884606 FGF18 5 171444070
rs4380013 USP8 15 50467231
rs4073 CXCL8 4 73740307
rs4264 TFPI2 7 93886765
rs4548913 SRR 17 2306594
rs4775006 - 15 57923529
rs551471509 - 19 9832588
rs4590360 TBXAS1 7 139828863
rs4888378 CFDP1 16 75298143
rs571734653 DGKI 7 137458951
rs58973023 - 13 42384997
rs59163323 - 4 1761591
rs4977574 CDKN2B-AS1 9 22098575
rs59805398 TFPI2 7 93891949
rs6074022 - 20 46111557
rs6500609 NMRAL1 16 4465333
rs66906321 - 2 630070
rs6434222 TFPI 2 187547517
rs6801836 AGTR1 3 148737750
rs72760655 COL27A1 9 114153934
rs72979233 POLD3 11 74644478
rs74676797 - 2 633063
rs689466 PTGS2 1 186681619
rs7586970 TFPI 2 187478770
rs7581446 LTBP1 2 33198734
rs763780 IL17F 6 52236941
rs7680647 - 4 1748760
rs9349379 PHACTR1 6 12903725
rs7953280 CRADD 12 93742233
rs7967762 LOC105369750 12 48026431
rs80308593 LOC105376205 9 107641521
rs9270986 - 6 32606283
rs9908159 - 17 56764600
rs9940278 FTO 16 53766288
表3 部分统计结果
rs ID 基因频率（全球人口） 基因频率（对照组） 基因频率（KOA组） 基因频率（KOA-AS组） 对照 KOA组 KOA-AS组 P值
rs1426371 A=0.616；G=0.384 A=0.286；G=0.714 A=0.864；G=0.136 A=0.643；G=0.357 AG（4）；GG（3） AA（8）；AG（3） AA（4）；AG（10） ＜0.001
rs3842788 A=0.0603；G=0.9397 A=0.0625；G=0.9375 A=0.227；G=0.773 A=0；G=1 GG（7）；GA（1） GG（6）；GA（5） GG（14） 0.006
rs10842226 A=0.806；G=0.19 A=0.8125；G=0.1875 A=0.955；G=0.045 A=0.75；G=0.25 AA（5）；AG（3） AA（10）；GG（1） AA（7）；AG（7） 0.017
rs2229080 G=0.42；C=0.58 G=0.4375；C=0.5625 G=0.545；C=0.455 G=0.357；C=0.643 GC（7）；CC（1） GG（5）；GC（2）；CC（4） GG（1）；GC（8）；CC（5） 0.009
图1 rs1426371关联疾病富集结果
图2 代谢组学生物信息学分析。图a为QC样本Spearman相关系数热图；图b为QC样本检出代谢物类别分布条形图；图c为对照组-KOA组-KOA-AS组中代谢物水平依次升高的KEGG富集分析；图d为对照组-KOA组-KOA-AS组中代谢物水平依次下降的KEGG富集分析 注：QC为质量控制；KOA为膝骨关节炎；AS为动脉硬化；KEGG为京都基因与基因组百科全书
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