卵巢早衰患者血清TNF-α、TGF-β1水平及TNF-α基因308G/A位点多态性分析

Association between levels of TNF-α,TGF-β1 and the polymorphism of TNF-α gene 308G/A in patients with premature ovarian failure

为了解卵巢早衰(premature ovarian failure,POF)患者TNF-α基因308G/A位点单核苷酸多态性(single nucleotide polymorphisms,SNP)的分布特征及其与TNF-α、TGF-β1水平之间的相关性,选取2017年4月—2019年5月来深圳龙华区人民医院妇产中心就诊并确诊为POF患者167例为POF组,选择同期非POF健康育龄妇女120例为对照组,采用ELISA检测血清TNF-α、TGF-β1水平,同时应用PCR-限制性片段长度多态性(restriction fragment length polymorphism,RFLP)法检测TNF-α基因308G/A位点多态性。结果显示,POF患者血清TNF-α和TGF-β1水平分别为(9.02±3.28) pg/mL和(197.24±18.75) pg/mL,明显低于对照组[(21.59±6.86) pg/mL和(463.69±62.54) pg/mL](均P<0.05);POF患者血清TNF-α基因308G/A位点GG基因型及G等位基因检出率分别为85.03%和90.12%,明显高于对照组(62.50%和73.33%)(均P<0.05);TNF-α基因308G/A位点GG基因型的POF患者血清TNF-α和TGF-β1水平分别为(8.24±3.06) pg/mL和(172.57±15.04) pg/mL,明显低于GA基因型[(11.85±4.07) pg/mL和(292.98±37.60) pg/mL]和AA基因型[(16.67±7.15) pg/mL和(431.67±58.49) pg/mL](均P<0.05)。该研究提示,POF患者血清TNF-α和TGF-β1表达水平明显降低,且TNF-α基因308G/A位点多态性与TNF-α、TGF-β1水平存在一定的相关性,可能是导致POF的危险遗传基因之一。

We aimed to investigate the single nucleotide polymorphism( SNP) of 308 G/A site of TNF-α gene and its relationship to the serum level of TNF-α and TGF-β1 in patients with premature ovarian failure( POF). One hundred sixty-seven patients with POF and 120 women of non-POF healthy childbearing age were collected. The levels of TNF-α,TGF-β1 in serum were detected by ELISA and PCR-restriction fragment length polymorphism( RFLP) method was carried out to detect the SNP of TNF-α gene 308 G/A site.The results showed that serum levels of TNF-α and TGF-β1 in the POF group were( 9.02±3.28) pg/mL and( 197.24±18.75) pg/mL,respectively,which were significantly lower than those in the control group [( 21.59± 6.86) pg/mL,( 463.69± 62.54) pg/mL ]( P< 0.05). The frequencies of GG genotype and G allele at the TNF-α gene 308 G/A site in serum of POF patients were 85.03% and 90.12%,respectively,which were significantly higher than those of the control group( 62.50% and 73.33%)( P<0.05). The serum levels of TNF-α and TGF-β1 in the POF group with GG geno-type at the 308 G/A site were( 8.24± 3.06) pg/mL and( 172.57± 15.04) pg/mL,respectively,which were significantly lower than those with GA [( 11.85± 4.07) pg/mL,( 292.98± 37.60) pg/mL ]and AA genotypes [( 16.67±7.15) pg/mL,( 431.67±58.49) pg/mL ]( P<0.05). Altogether,in POF patients,serum levels of TNF-α and TGF-β1 are significantly decreased,which is associated with 308 G/A site polymorphism of TNF-α gene. This study suggests that TNF-α gene might be one of the risk genes for POF.