SF1 和 WNT4 基因突变筛查在突尼斯卵巢早衰女性中的应用。
Mutational screening of SF1 and WNT4 in Tunisian women with premature ovarian failure.
机构信息
Cytogenetics and Biology Department, Farhat Hached University Teaching Hospital, Sousse, Tunisia.
出版信息
Gene. 2012 Nov 10;509(2):298-301. doi: 10.1016/j.gene.2012.08.007. Epub 2012 Aug 23.
BACKGROUND
WNT4 and SF1 genes play an important role in ovarian development. They constitute coherent candidate genes associated with premature ovarian failure (POF) pathogenesis.
METHODS
We sequenced the coding region of WNT4 and SF1 in 55 Tunisian women with POF and 100 healthy controls.
RESULTS
We identified a synonymous variation in WNT4 (c.99G>A, p.Ser33Ser) and a substitution (c.G437C) in SF1 gene inducing G146 to Ala (GGG-GCG) missense mutation. WNT4 (c.99G>A, p.Ser33Ser) was not associated with POF pathology. However, a positive association of SF1 Gly146Ala polymorphism was noted. Gly146Ala minor allele frequency was significantly higher (p=0.029) in POF patients versus controls and Ala allele containing genotypes (p=0.005) were positively associated with POF pathology. The carriage of 146Ala allele was also associated with a significant reduction in estradiol plasma levels.
CONCLUSIONS
SF1 Gly146Ala polymorphism seems to be associated with POF pathology in the Tunisian population likely by reducing estradiol levels.
背景
WNT4 和 SF1 基因在卵巢发育中起着重要作用。它们构成了与卵巢早衰（POF）发病机制相关的一致候选基因。
方法
我们对 55 名突尼斯 POF 女性和 100 名健康对照者的 WNT4 和 SF1 编码区进行了测序。
结果
我们在 WNT4 基因中发现了一个同义变异（c.99G>A，p.Ser33Ser）和 SF1 基因中的一个取代（c.G437C），导致 G146 突变为 Ala（GGG-GCG）错义突变。WNT4（c.99G>A，p.Ser33Ser）与 POF 病理无关。然而，SF1 Gly146Ala 多态性与 POF 存在正相关。POF 患者的 Gly146Ala 等位基因频率明显高于对照组（p=0.029），并且含有 Ala 等位基因的基因型（p=0.005）与 POF 病理呈正相关。携带 146Ala 等位基因也与雌二醇血浆水平的显著降低有关。
结论
SF1 Gly146Ala 多态性似乎与突尼斯人群的 POF 病理有关，可能是通过降低雌二醇水平。
Zotero 插件