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。
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.
关键词
SPOCK基因 /
TMEM38B基因 /
单核苷酸多态性 /
月经初潮年龄
Key words
SPOCK gene /
TMEM38B gene /
single nucleotide polymorphisms /
age at menarche
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基金
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)
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