示-环指长比与6个指骨发育相关基因多态性的关联性

杨梦怡; 牛世博; 张静; 彭亮; 党洁; 马占兵; 陆宏; 霍正浩

doi:10.16098/j.issn.0529-1356.2024.02.008

PDF(1008 KB)

解剖学报 ›› 2024, Vol. 55 ›› Issue (2) : 181-187. DOI: 10.16098/j.issn.0529-1356.2024.02.008

细胞和分子生物学

示-环指长比与6个指骨发育相关基因多态性的关联性

杨梦怡牛世博张静彭亮党洁马占兵陆宏* 霍正浩*

作者信息 +

Association between index-ring finger length ratio and polymorphisms of 6 phalange-bone development related genes

YANG Meng-yi NIU Shi-bo ZHANG Jing PENG Liang DANG Jie MA Zhan-bing LU Hong* HUO Zheng-hao*

Author information +

文章历史 +

摘要

目的探讨6个指骨发育相关基因，即成纤维细胞生长因子受体2(FGFR2)、印度刺猬信号分子(IHH)、Msh同源盒1(MSX1)、Runx家族转录因子2(RUNX2)、SRY盒转录因子9(SOX9)及Wnt家族成员5A（WNT5A）13个位点单核苷酸多态性（SNP）与人类示-环指长比（2D∶4D）的关联性。方法采用数码相机拍摄宁夏地区731名在校大学生（男性358名，女性373名）手部正面照片，采用GraphPad Prism 8.0图像分析软件标记解剖点并测量示（2）指及环（4）指指长；多重PCR法进行6个基因13个SNP位点（rs1047057、rs755793、rs41258305、rs3731881、rs3100776、rs12532、rs3821949、rs45585135、rs3749863、rs1042667、rs12601701、rs1829556和rs3732750）的基因分型；单因素方差分析或独立样本t检验间接评估2D∶4D与13个SNP位点间的关联性。结果宁夏大学生女性左手和右手2D∶4D均显著高于男性（均P<0.01）；13个SNP位点基因型、等位基因频率在不同性别间的差异均无显著统计学意义（均P>0.05）；不同性别中，男性左手2D∶4D与SOX9基因rs12601701位点基因型显著关联（P<0.05），右手2D∶4D与WNT5A基因rs1829556位点基因型显著关联（P<0.05）；女性右手2D∶4D与MSX1基因rs12532（P<0.01）和rs3821949（P<0. 05）位点基因型显著关联。结论 SOX9 （rs12601701）、WNT5A （rs1829556）、MSX1（rs12532和rs3821949）基因多态性可能与宁夏地区人群2D∶4D的形成有关。

Abstract

Objective To investigate the association of 13 single nucleotide polymorphism (SNP) sites in 6 phalange-bone development related genes ［fibroblast growth factor receptor 2 (FGFR2), indian hedgehog signaling molecule (IHH), Msh homeobox 1(MSX1), Runx family transcription factor 2(RUNX2), SRY-box transcription factor 9(SOX9), Wnt family member 5A (WNT5A)］ with human index-ring finger length ratio (2D∶4D). Methods Digital cameras were used to take frontal photographs of the hands of 731 college students (358 males and 373 females) in Ningxia, and image analysis software was used to mark anatomical points and measure finger lengths of index (2th) and ring (4th); genotyping of 13 SNP sites (rs1047057, rs755793, rs41258305, rs3731881, rs3100776, rs12532, rs3821949, rs45585135, rs3749863, rs1042667, rs12601701, rs1829556, rs3732750) for 6 genes by multiplex PCR; One-Way ANOVA or independent sample t-test indirectly assessed the association between 2D∶4D and 13 SNP sites. Results Both left and right hand 2D∶4D were significantly higher in females than males in Ningxia college students (all P<0.01); no statistically significant differences in genotype and allele frequencies of the 13 SNP sites among different sexes (all P>0.05); among different sexes, male left hand 2D∶4D was significantly associated with the genotype of SOX9 gene rs12601701 site (P<0.05) and right hand 2D∶4D was significantly associated with the genotype of WNT5A gene rs1829556 site (P<0.05); the female right hand 2D∶4D was significantly associated with the MSX1 gene rs12532 (P<0.01) and rs3821949 (P<0.05) sites genotypes. Conclusion SOX9 (rs12601701), WNT5A (rs1829556) and MSX1 (rs12532 and rs3821949) gene polymorphisms may be associated with the formation of 2D∶4D in Ningxia population.

导出引用

杨梦怡牛世博张静彭亮党洁马占兵陆宏霍正浩. 示-环指长比与6个指骨发育相关基因多态性的关联性[J]. 解剖学报. 2024, 55(2): 181-187 https://doi.org/10.16098/j.issn.0529-1356.2024.02.008

YANG Meng-yi NIU Shi-bo ZHANG Jing PENG Liang DANG Jie MA Zhan-bing LU Hong HUO Zheng-hao. Association between index-ring finger length ratio and polymorphisms of 6 phalange-bone development related genes[J]. Acta Anatomica Sinica. 2024, 55(2): 181-187 https://doi.org/10.16098/j.issn.0529-1356.2024.02.008

中图分类号： Q983

参考文献

［1］Manning JT, Fink B, Mason L, et al. Digit ratio (2D∶4D) and body mass index in the BBC internet study: prenatal sex steroids and a Trivers-Willard effect on body composition［J］. J Biosoc Sci, 2022, 54(5): 902-911.

［2］Swift-Gallant A, Shirazi T, Puts D A, et al. Evidence for perinatal steroid influence on human sexual orientation and gendered behavior［J］. Cold Spring Harb Perspect Biol, 2022, 14(8):1-14.

［3］Fusar-Poli L, Rodolico A, Sturiale S, et al. Second-to-fourth digit ratio (2D∶4D) in psychiatric disorders: a systematic review of case-control studies［J］. Clin Psychopharmacol Neurosci, 2021, 19(1): 26-45.

［4］Adamczyk JG, Safranow K, Gajewski AK, et al. The second-to-fourth digit (2D∶4D) ratio of male combat athletes is associated with the choice of sport［J］. J Hum Kinet, 2021, 78(1): 59-66.

［5］Zheng Z, Cohn MJ. Developmental basis of sexually dimorphic digit ratios［J］. Proc Natl Acad Sci USA, 2011, 108(39): 16289-16294.

［6］Lawrance-Owen AJ, Bargary G, Bosten JM, et al. Genetic association suggests that SMOC1 mediates between prenatal sex hormones and digit ratio［J］. Hum Genet, 2013, 132(4): 415-421.

［7］Zhang J, Yang MY, Luan PF, et al. Associations between cytochrome P450 (CYP) gene single-nucleotide polymorphisms and second-to-fourth digit ratio in chinese university students［J］. Med Sci Monit, 2021, 27(3): 930591-930604.

［8］Xi HJ, Zhao H, Li WH, et al. Primary analysis of current studies on the digit ratio［J］. Acta Anatomica Sinica, 2012, 43(4): 569-573. ( in Chinese)

席焕久，赵红，李文慧，等. 对指长比研究现状的初步分析［J］. 解剖学报, 2012, 43(4): 569-573.

［9］Fonseca C, Martelli D, Maia C, et al. Digital biomarker 2D∶4D as a predictor of cancer: a systematic review［J］. Early Hum Dev, 2022, 164(1): 105521-105532.

［10］Zhanbing M, Jie D, Chunyue B, et al. Association of CYP19A1 single-nucleotide polymorphism with digit ratio (2D∶4D) in a sample of men and women from Ningxia (China)［J］. Early Hum Dev, 2019, 132(4): 58-65.

［11］Medland SE, Zayats T, Glaser B, et al. A variant in LIN28B is associated with 2D∶4D finger-length ratio, a putative retrospective biomarker of prenatal testosterone exposure［J］. Am J Hum Genet, 2010, 86(4): 519-525.

［12］Lefebvre V, Angelozzi M, Haseeb A. SOX9 in cartilage development and disease［J］. Curr Opin Cell Biol, 2019, 61(6): 39-47.

［13］Akiyama H, Stadler HS, Martin JF, et al. Misexpression of Sox9 in mouse limb bud mesenchyme induces polydactyly and rescues hypodactyly mice［J］. Matrix Biol, 2007, 26(4): 224-233.

［14］Liu M, Zhang X, Liu H, et al. A 17q24-3 duplication identified in a large Chinese family with brachydactyly-anonychia［J］. Mol Genet Genomic Med, 2020, 8(9): 1392-1397.

［15］Gros J, Hu JK, Vinegoni C, et al. WNT5A/JNK and FGF/MAPK pathways regulate the cellular events shaping the vertebrate limb bud［J］. Curr Biol, 2010, 20(22): 1993-2002.

［16］Yamaguchi TP, Bradley A, Mcmahon AP, et al. A Wnt5a pathway underlies outgrowth of multiple structures in the vertebrate embryo［J］. Development, 1999, 126(6): 1211-1223.

［17］Farrera-Hernandez A, Marin-Llera JC, Chimal-Monroy J. WNT5A-Ca²⁺-CaN-NFAT signalling plays a permissive role during cartilage differentiation in embryonic chick digit development［J］. Dev Biol, 2021, 469(1): 86-95.

［18］Abu-Ghname A, Trost J, Davis MJ, et al. Extremity anomalies associated with Robinow syndrome［J］. Am J Med Genet A, 2021, 185(12): 3584-3592.

［19］Yang Y, Zhu X, Jia X, et al. Phosphorylation of Msx1 promotes cell proliferation through the Fgf9/18-MAPK signaling pathway during embryonic limb development［J］. Nucleic Acids Res, 2020, 48(20): 11452-11467.

［20］Bensoussan-Trigano V, Lallemand Y, Saint CC, et al. Msx1 and Msx2 in limb mesenchyme modulate digit number and identity［J］. Dev Dyn, 2011, 240(5): 1190-1202.

［21］Allan CH, Fleckman P, Fernandes RJ, et al. Tissue response and Msx1 expression after human fetal digit tip amputation in vitro［J］. Wound Repair Regen, 2006, 14(4): 398-404.

［22］Wattanarat O, Kantaputra PN. Preaxial polydactyly associated with a MSX1 mutation and report of two novel mutations［J］. Am J Med Genet A, 2016, 170A(1): 254-259.

［23］Zu G, Gao J, Zhou T. The clinico pathological and prognostic significance of SOX9 expression in gastric cancer: meta-analysis and TCGA analysis［J］. Front Oncol, 2021, 11(1): 668946-668955.

［24］Ren D, Dai Y, Yang Q, et al. Wnt5a induces and maintains prostate cancer cells dormancy in bone［J］. J Exp Med, 2019, 216(2): 428-449.

［25］Rohmann E, Brunner HG, Kayserili H, et al. Mutations in different components of FGF signaling in LADD syndrome［J］. Nat Genet, 2006, 38(4): 414-417.

［26］Zhou J, Meng J, Guo S, et al. IHH and FGF8 coregulate elongation of digit primordia［J］. Biochem Biophys Res Commun, 2007, 363(3): 513-518.

［27］Yoshida CA, Yamamoto H, Fujita T, et al. Runx2 and Runx3 are essential for chondrocyte maturation, and Runx2 regulates limb growth through induction of Indian hedgehog［J］. Genes Dev, 2004, 18(8): 952-963.