SPOCK、TMEM38B基因多态性与肃南地区女童月经初潮年龄的相关性研究

doi:10.11852/zgetbjzz2025-0112

中国儿童保健杂志 ›› 2025, Vol. 33 ›› Issue (12): 1291-1297.DOI: 10.11852/zgetbjzz2025-0112

SPOCK、TMEM38B基因多态性与肃南地区女童月经初潮年龄的相关性研究

张宗翠¹, 马薇¹, 张红晓², 王玲³, 刘金英¹, 马文元⁴, 石蕊¹, 张羽¹

1.西北民族大学医学部,甘肃兰州 730030;
2.兰州大学第二医院儿童保健科;
3.中国人民解放军联勤保障部队第九四〇医院生殖医学中心;
4.肃南县卫生健康局

收稿日期:2025-02-12 修回日期:2025-06-24 发布日期:2025-12-02 出版日期:2025-12-10
通讯作者: 马薇,E-mail:615269351@qq.com
作者简介:张宗翠(1997—),女,硕士研究生在读,主要研究方向为高原地区女童性早熟相关因素。
基金资助:
中央高校基本科研业务费项目(31920200001);国家自然科学基金项目(81460498);2025年甘肃省高校研究生“创新之星”项目(2025CXZX-240)

Correlation of SPOCK and TMEM38B gene polymorphisms with age at menarche in girls from the Sunan region

ZHANG Zongcui¹, MA Wei¹, ZHANG Hongxiao², WANG Ling³, LIU Jinying¹, MA Wenyuan⁴, SHI Rui¹, ZHANG Yu¹

1. School of Medicine, Northwest Minzu University, Lanzhou,Gansu 730030, China;
2. Department of Child Health Care, The Second Hospital of Lanzhou University;
3. Reproductive Medicine Center, the 940th Hospital of Joint Logistic Support Force of Chinese People′s Liberation Army;
4. Sunan County Health Bureau

Received:2025-02-12 Revised:2025-06-24 Online:2025-12-10 Published:2025-12-02
Contact: MA Wei,E-mail:615269351@qq.com

摘要/Abstract

摘要： 目的探究SPOCK、TMEM38B基因多态性与肃南地区女童月经初潮年龄(AAM)的相关性,为预防AAM提前提供科学依据。方法 2023年1—7月抽取甘肃省张掖市裕固族自治县159名9~18岁女生为研究对象。根据AAM的百分位数(P₂₅=12.8岁),分为提前组(AAM<12.8岁,n=75)和正常组(n=84)。从NCBI和千人基因组计划项目的共享资源网站下载候选基因SPOCK、TMEM38B的所有SNP位点。使用Haploview 软件筛选出最小等位基因频率(MAF)＞0.05的位点,并进行连锁不平衡分析,最终确定TagSNP。采用多因素logistic回归分析不同遗传模型下SNP位点与AAM提前风险的相关性。结果在调整混杂因素后,SPOCK1基因的rs1859345(超显性模型:TC vs. TT+CC, OR=2.10, 95%CI: 1.01~4.42, P=0.046)和rs7701979(超显性模型:GT vs. GG+TT, OR=2.18, 95%CI: 1.02~4.65, P=0.040)位点与AAM提前风险显著相关。TMEM38B基因的rs10453225(共显性模型:GT vs. GG, OR=2.83, 95%CI: 1.29~6.20, P=0.024;显性模型:GT+TT vs. GG, OR=2.38, 95%CI: 1.13~4.98, P=0.020; 超显性模型:GT vs. GG+TT, OR=2.30, 95%CI: 1.21~4.40, P=0.011)、rs4452860(隐性模型:AA vs. GG+GA, OR=0.43, 95%CI: 0.20~0.94, P=0.033;超显性模型:GA vs. GG+AA, OR=2.13, 95%CI: 1.12~4.07, P=0.021)和rs12684013(超显性模型:CT vs. TT+CC, OR=1.96, 95%CI: 1.04~3.73, P=0.037)位点同样与AAM提前风险显著相关。结论 SPOCK的rs1859345位点、rs7701979位点,TMEM38B的rs10453225位点、rs4452860位点、rs12684013位点均与肃南地区女生AAM存在相关性,提示这些基因可能在月经初潮的遗传调控中发挥作用,为AAM提前的早期筛查提供了潜在的遗传标记。

关键词: SPOCK基因, TMEM38B基因, 单核苷酸多态性, 月经初潮年龄

Abstract: Objective To investigate the association between single nucleotide polymorphisms (SNPs) in the SPOCK1 and TMEM38B genes and early age at menarche (AAM) in girls from the Sunan region of Gansu Province, so as to provide evidence for the prevention of early AAM. Methods From January to July 2023, 159 menstruated girls aged 9 - 18 from Yugur Autonomous County, Zhangye City, Gansu Province were recruited. Participants were divided into an early AAM group (AAM<12.8 years, n=75) and a normal AAM group (n=84) based on the 25th percentile(12.8 years old)of their AAM. TagSNPs for the candidate genes SPOCK1 and TMEM38B were selected from public NCBI and the shared resources of the 1 000 Genomes Project. Haploview software was used to screen out loci with a minimum allele frequency (MAF) of >0.05, and linkage disequilibrium analysis was performed to finalize the TagSNP. Multivariate logistic regression was used to analyze the association between SNPs and the risk of early AAM under different genetic models. Results After adjusting for confounders, significant associations with early AAM risk were found for SPOCK1 gene SNPs rs1859345 (overdominant model: TC vs. TT+CC, OR=2.10, 95%CI: 1.01 - 4.42, P=0.046) and rs7701979 (overdominant model: GT vs. GG+TT, OR=2.18, 95%CI: 1.02 - 4.65, P=0.040). Significant associations were also identified for TMEM38B gene SNPs rs10453225 (codominant model: GT vs. GG, OR=2.83, 95%CI: 1.29 - 6.20, P=0.024; dominant model: GT+TT vs. GG, OR=2.38, 95%CI: 1.13 - 4.98, P=0.020; overdominant model: GT vs. GG+TT, OR=2.30, 95%CI: 1.21 - 4.40, P=0.011), rs4452860 (recessive model: AA vs. GG+GA, OR=0.43, 95%CI: 0.20 - 0.94, P=0.033; overdominant model: GA vs. GG+AA, OR=2.13, 95%CI: 1.12 - 4.07, P=0.021), and rs12684013 (overdominant model: CT vs. TT+CC, OR=1.96, 95%CI: 1.04 - 3.73, P=0.037). Conclusion The rs1859345 and rs7701979 loci of SPOCK gene, and the rs10453225 locus, rs4452860 locus and rs12684013 locus of TMEM38B gene are all correlated with AAM in girls in Sunan region, suggesting these genes may play a role in the genetic regulation of menarche and providing potential genetic markers for the early screening of early AAM.

Key words: SPOCK gene, TMEM38B gene, single nucleotide polymorphisms, age at menarche

中图分类号:

R179

张宗翠, 马薇, 张红晓, 王玲, 刘金英, 马文元, 石蕊, 张羽. SPOCK、TMEM38B基因多态性与肃南地区女童月经初潮年龄的相关性研究[J]. 中国儿童保健杂志, 2025, 33(12): 1291-1297.

ZHANG Zongcui, MA Wei, ZHANG Hongxiao, WANG Ling, LIU Jinying, MA Wenyuan, SHI Rui, ZHANG Yu. Correlation of SPOCK and TMEM38B gene polymorphisms with age at menarche in girls from the Sunan region[J]. Chinese Journal of Child Health Care, 2025, 33(12): 1291-1297.

参考文献

[1] Rivas PM, Torres MB, Torres CN. Age of the onset of menarche and its complications: A literature review[J]. Int J Gynaecol Obstet, 2023,162(1):244-255.
[2] Bertomeu-Gonzalez V, Cordero A, Ruiz-Nodar JM, et al. Risk factors for major adverse cardiovascular events in postmenopausal women: UK Biobank prospective cohort study[J]. Atherosclerosis, 2023,386:117372.
[3] Gong J, Harris K, Peters S, et al. Reproductive factors and the risk of incident dementia: A cohort study of UK Biobank participants[J]. PLoS Med, 2022,19(4):e1003955.
[4] Long C, Benny P, Yap J, et al. A systematic review of genetics and reproductive health outcomes: Asian perspective[J]. Reprod Sci, 2024,31(2):309-319.
[5] Tsinopoulou VR, Bacopoulou F, Fidani S, et al. Genetic determinants of age at menarche: Does the LIN28B gene play a role? A narrative review[J]. Hormones (Athens), 2025,24(1):167-177.
[6] Day FR, Thompson DJ, Helgason H, et al. Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk[J].Nat Genet, 2017,49(6):834-841.
[7] Busch AS, Hagen CP, Assens M, et al.Differential impact of genetic loci on age at thelarche and menarche in healthy girls[J]. J Clin Endocrinol Metab, 2018,103(1):228-234.
[8] 孟鑫.中国青少年女性月经初潮年龄变化趋势及影响因素的研究[D].济南:山东大学, 2018.
Meng X. A study on the trend and influencing factors of menarche age in Chinese adolescent girls[D].Jinan:Shandong University,2018.(in Chinese)
[9] Ma N, Shi D, Dang JJ, et al. Secular trends and urban-rural disparities in the median age at menarche among Chinese han girls from 1985 to 2019[J]. World J Pediatr, 2023,19(12):1162-1168.
[10] Zhou S, Xu Y, Xiong J, et al. Cross-trait multivariate GWAS confirms health implications of pubertal timing[J]. Nat Commun, 2025,16(1):799.
[11] Xiang Y, Tanwar V, Singh P, et al. Early menarche and childbirth accelerate aging-related outcomes and age-related diseases: Evidence for antagonistic pleiotropy in humans[J]. Elife, 2025,13:RP102447.
[12] 海波, 沈蕙, 邴鹏飞, 等. 苏州市中小学女生超重肥胖与月经初潮年龄提前的相关性研究[J]. 中国初级卫生保健, 2022,36(2):101-102.
Hai B,Shen H,Bing PF, et al. Correlation between overweight and obesity and earlier age of menarche among schoolgirls in Suzhou[J].Chin J Primary Health Care,2022,36(2):101-102.(in Chinese)
[13] Oyama S, Duckham RL, Pomer A, et al. Association between age at menarche and cardiometabolic risk among Samoan adults[J]. Am J Hum Biol, 2024,36(1):e23982.
[14] Dong B, Zhi M, Han M, et al.Early menarche is associated with insulin resistance in advanced maternal age before delivery[J]. Gynecol Endocrinol, 2020,36(4):341-345.
[15] Tinano FR, Machado I, Latronico AC, et al. Shared pathophysiological mechanisms and genetic factors in early menarche and polycystic ovary syndrome[J].J Neurosci,2025,45(11): e1681242024.
[16] Wang L, Song L, Liu B, et al. Earlier maternal menarche is associated with shorter newborn telomere length[J]. Eur J Pediatr, 2020,179(10):1507-1513.
[17] Sun LR, Li SY, Guo QS, et al. SPOCK1 involvement in epithelial-to-mesenchymal transition: A new target in cancer therapy?[J]. Cancer Manag Res, 2020,12:3561-3569.
[18] Liu YZ, Guo YF, Wang L, et al. Genome-wide association analyses identify SPOCK as a key novel gene underlying age at menarche[J].PLoS Genet, 2009,5(3):e1000420.
[19] Boizet-Bonhoure B, Dejardin S, Girard M, et al. Adenomyotic lesions are induced in the mouse uterus after exposure to NSAID and EE2 mixtures at environmental doses[J].Int J Mol Sci, 2024,25(4):2003.
[20] Tsai MC, Hsu CH, Chu SK, et al. Genome-wide association study of age at menarche in the Taiwan Biobank suggests NOL4 as a novel associated gene[J]. J Hum Genet, 2023,68(5):339-345.
[21] Kang H, Lee CJ. Transmembrane proteins with unknown function (TMEMs) as ion channels:Electrophysiological properties, structure, and pathophysiological roles[J].Exp Mol Med, 2024,56(4):850-860.
[22] Jovanovic M, Mitra A, Besio R, et al. Absence of TRIC-B from type XIV osteogenesis imperfecta osteoblasts alters cell adhesion and mitochondrial function-A multi-omics study[J].Matrix Biol, 2023,121:127-148.
[23] Mehta P, Vishvkarma R, Gupta S, et al. Exome sequencing identified mutations in the WNT1 and COL1A2 genes in osteogenesis imperfecta cases[J]. Mol Biol Rep, 2024,51(1):449.
[24] 马超.基于SSCs/OCs探讨木豆异黄酮预防骨质疏松症形成的作用机制[D].广州:广州中医药大学, 2024.
Ma C.Exploring the Mechanism of Cajanin in preventing osteoporosis formation based on SSCs/OCs[D].Guanzhou:Guangzhou University of Traditional Chinese Medicine,2024.(in Chinese)

SPOCK、TMEM38B基因多态性与肃南地区女童月经初潮年龄的相关性研究

Correlation of SPOCK and TMEM38B gene polymorphisms with age at menarche in girls from the Sunan region

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