TNF-α遺伝子T-1031C多型と子宮内膜症との関連。メタアナリシス

Association of TNF-α gene T-1031C polymorphism with endometriosis: A Meta-Analysis.

• Xian-Ling Cao
• Jie Chai
• Yang-Yang Yu
• Xiao Tian
• Jian-Yun Zhao
• Ling-Yu Yu
• Zhen-Gao Sun

抄録

一塩基多型T-1031Cは、TNF-α遺伝子の制御と転写効率に重要な役割を持つことが示されている。しかし、TNF-α T-1031C遺伝子多型と子宮内膜症(EM)の発症との関係はいまだに不明である。本メタアナリシスの目的は、TNF-α T-1031C遺伝子多型の影響をまとめ、子宮内膜症との関連を明らかにすることである。PubMed、EMBASE、Web of Science、Cochrane central register of controlled trials（2019年8月10日まで）を用いて包括的な文献検索を行った。研究間の不均一性に応じて固定効果モデルまたはランダム効果モデルを採用した。対立遺伝子比較（T vs. C）、ホモ接合体比較（TT vs. CC）および（TC vs. CC）、優性（TT vs. TC + CC）、優性（TT vs. TC + CC）、超優性（TT+CC vs. TC）、劣性（TT + TC vs. CC）のモデルにおいて、Logオッズ比（LOR）および95％信頼区間（CI）を推定し、関連の強さを推定した。合計7件の症例対照研究がこのメタ解析に含まれた。全体的に、TNF-α T-1031C と EM の間に有意な関連が同定された（T vs. C.対数OR [95%CI] = 0.31 [-0.09, 0.71]；TT+CC vs. TC: 0.27 [0.04, 0.50]；TC+CC vs. TT: -0.83 [-1.19,-0.47]）から有意な相関が確認された。)一方、他の遺伝子モデルでは有意な相関は認められなかった（TT vs. TC：Log OR [95%CI]=0.89 [0.64,1.13]；TT vs. CC：0.3 [-0.74,1.36]；TT+TC vs. CC：0.17 [-0.81,1.15]）。民族性やHWEのp値によるサブグループ解析では、ヨーロッパ人ではドミナントモデル（TT vs. TC + CC: Log OR [95%]=-0.84[-1.60,-0.09]）、アジア人ではハイパードミナントモデル（TT+CC vs. TC: Log OR[95%]=0.24[0.001,0.49]）において、TNF-α T-1031C多型とEMの間に統計的に有意な関連が認められた。以上のことから、本メタ解析により、TNF-α T-1031C多型はEM感受性と関連し、アジア人および欧州人集団では保護効果があることが示された。

The single nucleotide polymorphism T-1031C has shown to have an important role in the regulation and transcription efficiency of TNF- α gene. Yet, the relationship between TNF-α T-1031C gene polymorphism and the development of endometriosis (EM) still remains unclear. The aim of this meta-analysis was to summarize the effects of TNF-α T-1031C gene polymorphism and clarify their possible association with EM. A comprehensive literature search was performed using PubMed, EMBASE, Web of Science, and the Cochrane central register of controlled trials (up to August 10, 2019). A fixed-or random-effects model was employed according to the heterogeneity among studies. The Log odds ratios (LORs) and 95% confidence intervals (CIs) were estimated in the models of allele comparison (T vs. C), homozygote comparison (TT vs. CC) and (TC vs. CC), dominant (TT vs. TC + CC), hyperdominant (TT+CC vs. TC) and recessive (TT + TC vs. CC) to estimate the strength of the associations. A total of 7 case-control studies were included in this meta-analysis. Overall, significant associations between TNF-α T-1031C and EM were identified from (T vs C: Log OR [95%CI] = 0.31 [-0.09, 0.71]; TT+CC vs. TC: 0.27 [0.04, 0.50]; TC+CC vs. TT: -0.83 [-1.19,-0.47]). On the other hand, no significant correlation was found in other gene models (TT vs. TC: Log OR [95%CI]=0.89 [0.64,1.13]; TT vs. CC: 0.3 [-0.74,1.36]; TT+TC vs. CC: 0.17 [-0.81,1.15]). In subgroup analyses by ethnicity or HWE p-value, there was a statistically significant association between TNF-α T-1031C polymorphisms and EM in the dominant model (TT vs. TC + CC: Log OR [95%]=-0.84[-1.60,-0.09]) for the European population, and in hyperdominant model (TT+CC vs. TC: Log OR[95%]=0.24[0.001,0.49]) for Asian population. To sum up, this meta-analysis showed that TNF-α T-1031C polymorphism was associated with EM susceptibility and has a protective effect in Asian and European populations.

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