目的:这里通过研究CβS(844ins68)的贡献来研究全身脉管系统与肿瘤生物学之间的联系,MTHFR(677C>T),NOS3(4a/4b),CYBA(C242T),和ACE1(I/D)基因对平滑肌瘤的发病,子宫和平滑肌瘤体积。
方法:通过PCR或PCR-RFLP对130名平滑肌瘤女性和527名健康女性的DNA样本进行基因分型。Qui-square(χ2)或Fisher精确检验用于检验相关性。所有上述测试均在IBM®SPSS®StatisticsVersion28中进行。统计显著性定义为p值<0.05。
结果:结果显示CβS(在共显性和等位基因模型中,p=0.044和,p=0.015,OR=1.791[1.114-2.879],分别),MTHFR(在共显性中,等位基因和显性模型,p=0.009,p=0.002,OR=0.585[0.416-0.824],p=0.003,OR=0.527[0.346-0.802],分别)和ACE1(主导模型,p=0.045,OR=0.639[0.411-0.992])基因与平滑肌瘤的发生有关。NOS34a4a基因型与较低的子宫体积相关(p=0.004)。这项研究还揭示了一些基因之间有趣的认识论相互作用,进一步强调了它们在疾病调节中的作用。的确,CC基因型(MTHFR)和(/)(CβS;p=0.003)之间的上位相互作用,4b4b(NOS3;p=0.006,OR=2.050[1.223-3.439])或DD(ACE1;p<0.001,OR=2.362[1.438-3.880])显示与该疾病相关,而4a的存在(NOS3)与I的存在(ACE1),增加了仅存在I等位基因的效应保护(p=0.029,OR=0.446[0.214-0.930])。
结论:我们得出结论,与全身血管系统相关的基因变异可能在平滑肌瘤的发生和发展中起作用。
OBJECTIVE: The link between the systemic vasculature system and tumor biology is here investigated by studying the contribution of CβS (844ins68), MTHFR (677C > T),
NOS3 (4a/4b), CYBA (C242T), and ACE1 (I/D) genes to leiomyoma onset, uterus and leiomyoma volumes.
METHODS: DNA samples from 130 women with leiomyomas and 527 from healthy women were genotyped by PCR or PCR-RFLP. Qui-square (χ2) or Fisher\'s exact test were used to test associations. All the mentioned tests were performed in IBM® SPSS® Statistics Version 28. Statistical significance was defined as a p-value < 0.05.
RESULTS: Results revealed that CβS (in the codominant and allelic models, p = 0.044 and, p = 0.015, OR = 1.791 [1.114-2.879], respectively), MTHFR (in the codominant, allelic and dominant models, p = 0.009, p = 0.002, OR = 0.585 [0.416-0.824] and p = 0.003, OR = 0.527 [0.346-0.802], respectively) and ACE1 (dominant model, p = 0.045, OR = 0.639 [0.411-0.992]) genes are associated with leiomyoma onset.
NOS3 4a4a genotype is associated with a lower uterus volume (p = 0.004). This study also uncovers intriguing epistatic interactions among some genes that further accentuate their roles in disease modulation. Indeed, the epistatic interactions between the CC genotype (MTHFR) and (+/+) (CβS; p = 0.003), 4b4b (
NOS3; p = 0.006, OR = 2.050 [1.223-3.439]) or DD (ACE1; p < 0.001, OR = 2.362 [1.438-3.880]) were shown to be associated with the disease, while 4a presence (
NOS3) in epistasis with I presence (ACE1), increased the effect protection having just the I allele presence (p = 0.029, OR = 0.446 [0.214-0.930]).
CONCLUSIONS: We conclude that variation in genes related to the systemic vascular system can play a role in the onset and development of leiomyoma.