Association between METTL14 gene polymorphisms and risk of ovarian endometriosis
BackgroundEndometriosis, a prevalent chronic gynecological condition, is frequently associated with infertility and pelvic pain. Despite numerous studies indicating a correlation between epigenetic regulation and endometriosis, its precise genetic etiology remains elusive. Methyltransferase-like 14...
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Frontiers Media S.A.
2025-01-01
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| author | Zijun Zhou Zijun Zhou Youkun Jie Xianyue Hu Xianyue Hu Guange Chen Yanjing Bao Yanjing Bao Zhenbo OuYang Liangzhi Wu Tianyang Gao Qiushi Zhang Qiushi Zhang Wenfeng Hua Wenfeng Hua |
| author_facet | Zijun Zhou Zijun Zhou Youkun Jie Xianyue Hu Xianyue Hu Guange Chen Yanjing Bao Yanjing Bao Zhenbo OuYang Liangzhi Wu Tianyang Gao Qiushi Zhang Qiushi Zhang Wenfeng Hua Wenfeng Hua |
| author_sort | Zijun Zhou |
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| description | BackgroundEndometriosis, a prevalent chronic gynecological condition, is frequently associated with infertility and pelvic pain. Despite numerous studies indicating a correlation between epigenetic regulation and endometriosis, its precise genetic etiology remains elusive. Methyltransferase-like 14 (METTL14), a crucial component of the N6-methyladenosine (m6A) RNA methyltransferase complex and an RNA binding scaffold, is known to play a pivotal role in various human diseases. The possibility that single nucleotide polymorphisms (SNPs) in the METTL14 gene contribute to susceptibility of endometriosis has not been thoroughly investigated.MethodsWe assessed the genotype frequencies of five potential functional METTL14 SNPs (rs298982 G>A, rs62328061A>G, rs9884978G>A, rs4834698C>T, and rs1064034A>T) in a Chinese population consisting of 458 patients with ovarian endometriosis and 462 healthy controls. We employed unconditional logistic regression and stratified analyses to evaluate their genotypic associations with the risk of ovarian endometriosis.ResultsAmong the five SNPs examined, we found that the rs298982 A allele was significantly associated with increased risk, whereas the rs62328061 G allele was linked to a decreased risk of ovarian endometriosis. Individuals harboring two unfavorable genotypes demonstrated a significantly elevated risk of ovarian endometriosis (adjusted odds ratio (AOR) = 1.57, 95% confidence interval (CI) = 1.16–2.13, P = 0.004) compared with those with no risk genotypes. Stratified analysis revealed the risk effect of rs298982 GA/AA genotypes in the gravidity≤1, parity≤1, rASRM stage I, and rASRM stage II + III + IVsubgroups. Haplotype analysis showed that individuals with the GATAA haplotype were at higher risk of ovarian endometriosis (AOR = 5.54, 95% CI = 1.63–18.87, P = 0.006), whereas the AGTTG haplotype exhibited protective effects (AOR = 0.55, 95% CI = 0.31–0.97, P = 0.039) compared with wild-type GACAG haplotype carriers. Additionally, Bayesian false discovery probability and false positive report probability analysis confirmed the robustness of the significant findings. Expression quantitative trait loci analysis revealed a significant association between the rs9884978 GA/AA genotypes and elevated METTL14 mRNA levels in fibroblasts and adrenal gland. Conversely, the rs298982 GA/GG genotypes were significantly associated with reduced METTL14 mRNA levels in the nucleus accumbens and frontal cortex.ConclusionOur results demonstrate that METTL14 polymorphisms are associated with susceptibility to ovarian endometriosis among Chinese women. |
| format | Article |
| id | doaj-art-517ea464f79f488d818091b79ad15453 |
| institution | Kabale University |
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| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-517ea464f79f488d818091b79ad154532025-01-03T06:47:32ZengFrontiers Media S.A.Frontiers in Genetics1664-80212025-01-011510.3389/fgene.2024.14602161460216Association between METTL14 gene polymorphisms and risk of ovarian endometriosisZijun Zhou0Zijun Zhou1Youkun Jie2Xianyue Hu3Xianyue Hu4Guange Chen5Yanjing Bao6Yanjing Bao7Zhenbo OuYang8Liangzhi Wu9Tianyang Gao10Qiushi Zhang11Qiushi Zhang12Wenfeng Hua13Wenfeng Hua14Department of Reproductive Medicine Center, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, Guangdong, ChinaDepartment of Gynecology and Obstetrics, The Third People’s Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, Chengdu, Sichuan, ChinaDepartment of Pathology, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi, ChinaThe Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, ChinaDepartment of Gynecology, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, Guangdong, ChinaDepartment of Gynecology and Obstetrics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaDepartment of Reproductive Medicine Center, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, Guangdong, ChinaThe Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, ChinaDepartment of Gynecology, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, Guangdong, ChinaDepartment of Gynecology, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, Guangdong, ChinaDepartment of Reproductive Medicine Center, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, Guangdong, ChinaDepartment of Gynecology, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, Guangdong, ChinaResearch Institute for Maternal and Child Health, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, Guangdong, ChinaDepartment of Gynecology, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, Guangdong, ChinaResearch Institute for Maternal and Child Health, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, Guangdong, ChinaBackgroundEndometriosis, a prevalent chronic gynecological condition, is frequently associated with infertility and pelvic pain. Despite numerous studies indicating a correlation between epigenetic regulation and endometriosis, its precise genetic etiology remains elusive. Methyltransferase-like 14 (METTL14), a crucial component of the N6-methyladenosine (m6A) RNA methyltransferase complex and an RNA binding scaffold, is known to play a pivotal role in various human diseases. The possibility that single nucleotide polymorphisms (SNPs) in the METTL14 gene contribute to susceptibility of endometriosis has not been thoroughly investigated.MethodsWe assessed the genotype frequencies of five potential functional METTL14 SNPs (rs298982 G>A, rs62328061A>G, rs9884978G>A, rs4834698C>T, and rs1064034A>T) in a Chinese population consisting of 458 patients with ovarian endometriosis and 462 healthy controls. We employed unconditional logistic regression and stratified analyses to evaluate their genotypic associations with the risk of ovarian endometriosis.ResultsAmong the five SNPs examined, we found that the rs298982 A allele was significantly associated with increased risk, whereas the rs62328061 G allele was linked to a decreased risk of ovarian endometriosis. Individuals harboring two unfavorable genotypes demonstrated a significantly elevated risk of ovarian endometriosis (adjusted odds ratio (AOR) = 1.57, 95% confidence interval (CI) = 1.16–2.13, P = 0.004) compared with those with no risk genotypes. Stratified analysis revealed the risk effect of rs298982 GA/AA genotypes in the gravidity≤1, parity≤1, rASRM stage I, and rASRM stage II + III + IVsubgroups. Haplotype analysis showed that individuals with the GATAA haplotype were at higher risk of ovarian endometriosis (AOR = 5.54, 95% CI = 1.63–18.87, P = 0.006), whereas the AGTTG haplotype exhibited protective effects (AOR = 0.55, 95% CI = 0.31–0.97, P = 0.039) compared with wild-type GACAG haplotype carriers. Additionally, Bayesian false discovery probability and false positive report probability analysis confirmed the robustness of the significant findings. Expression quantitative trait loci analysis revealed a significant association between the rs9884978 GA/AA genotypes and elevated METTL14 mRNA levels in fibroblasts and adrenal gland. Conversely, the rs298982 GA/GG genotypes were significantly associated with reduced METTL14 mRNA levels in the nucleus accumbens and frontal cortex.ConclusionOur results demonstrate that METTL14 polymorphisms are associated with susceptibility to ovarian endometriosis among Chinese women.https://www.frontiersin.org/articles/10.3389/fgene.2024.1460216/fullendometriosisinfertilitygene polymorphismMETTL14Chinese population |
| spellingShingle | Zijun Zhou Zijun Zhou Youkun Jie Xianyue Hu Xianyue Hu Guange Chen Yanjing Bao Yanjing Bao Zhenbo OuYang Liangzhi Wu Tianyang Gao Qiushi Zhang Qiushi Zhang Wenfeng Hua Wenfeng Hua Association between METTL14 gene polymorphisms and risk of ovarian endometriosis Frontiers in Genetics endometriosis infertility gene polymorphism METTL14 Chinese population |
| title | Association between METTL14 gene polymorphisms and risk of ovarian endometriosis |
| title_full | Association between METTL14 gene polymorphisms and risk of ovarian endometriosis |
| title_fullStr | Association between METTL14 gene polymorphisms and risk of ovarian endometriosis |
| title_full_unstemmed | Association between METTL14 gene polymorphisms and risk of ovarian endometriosis |
| title_short | Association between METTL14 gene polymorphisms and risk of ovarian endometriosis |
| title_sort | association between mettl14 gene polymorphisms and risk of ovarian endometriosis |
| topic | endometriosis infertility gene polymorphism METTL14 Chinese population |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2024.1460216/full |
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