Genetic predisposition of MTHFR and TNFSF4 gene polymorphism related to hypothyroidism– A meta-analysis

IF 1 Q4 GENETICS & HEREDITY

Gene Reports Pub Date : 2024-11-19 DOI:10.1016/j.genrep.2024.102091

Iyshwarya Bhaskar Kalarani , Karpagavel Lakshmanan , Ramakrishnan Veerabathiran

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Abstract

Background

Autoimmune thyroid diseases (AITDs), such as hypothyroidism, result from an intricate combination of genetic and environmental influences. The relationship between genetic variations in the MTHFR and TNFSF4 genes and autoimmune illnesses has been established, but their impact on hypothyroidism has not been well investigated. This study examines the associations between specific polymorphisms in the MTHFR (rs1801133) and TNFSF4 (rs3850641 and rs7514229) genes and the risk of hypothyroidism.

Methods

The study involved 168 hypothyroid patients and 171 healthy controls, all female and aged 18 to 45, from the Department of Obstetrics and Gynecology, Chettinad Academy of Research and Education in Chennai, India. Exclusion criteria included autoimmune thyroid diseases, pregnancy, medication use, and HIV positivity. Literature from PubMed, Cochrane Library, and Google Scholar, published between 2010 and 2024, was reviewed. Keywords included ‘MTHFR,’ ‘gene,’ ‘rs1801133,’ ‘AITD,’ and ‘Hypothyroidism.’ Heterogeneity was assessed using I² statistics, and the fixed or random effects model was applied accordingly. Sensitivity and publication bias were evaluated through various tests.

Results

The GA genotype and A allele were associated with increased hypothyroidism risk (OR = 0.55, 95 % CI: 0.35–0.89; OR = 0.62, 95 % CI: 0.40–0.94). The AA genotype did not significantly affect the MTHFR rs1801133 polymorphism. The G allele was associated with reduced hypothyroidism risk (OR = 0.67, 95 % CI: 0.47–0.97). No significant effects were found for genotype distributions or genetic models in TNFSF4 rs3850641, whereas the TNFSF4 rs7514229 polymorphism, the GT genotype, and the T allele were associated with reduced hypothyroidism risk (OR = 0.46, 95 % CI: 0.23–0.92; OR = 0.48, 95 % CI: 0.25–0.94). The dominant model revealed an elevated risk with GT+TT genotypes, and in the MTHFR rs1801133 polymorphism, the allelic model showed a significant link with hypothyroidism (OR = 1.49, 95 % CI: 0.99–2.22), while other genetic models did not demonstrate persistent significant correlations. A high degree of heterogeneity was identified.

Conclusion

The research discovered a strong correlation, particularly in the GA genotype and A allele, between the MTHFR rs1801133 polymorphism and the risk of hypothyroidism. Although some TNFSF4 polymorphisms showed associations with hypothyroidism, their overall impact was modest. Future research should include more significant, more diverse populations to understand better these genetic risk factors and their implications for hypothyroidism prevention and management.

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与甲状腺功能减退症有关的 MTHFR 和 TNFSF4 基因多态性遗传易感性--一项荟萃分析

背景自身免疫性甲状腺疾病（AITD），如甲状腺功能减退症，是遗传和环境影响错综复杂的综合结果。MTHFR和TNFSF4基因的遗传变异与自身免疫性疾病之间的关系已经确定，但它们对甲状腺功能减退症的影响尚未得到很好的研究。本研究探讨了 MTHFR（rs1801133）和 TNFSF4（rs3850641 和 rs7514229）基因中的特定多态性与甲状腺功能减退症风险之间的关联。研究对象包括 168 名甲状腺功能减退症患者和 171 名健康对照者，均为女性，年龄在 18 至 45 岁之间，来自印度钦奈 Chettinad 研究与教育学院妇产科。排除标准包括自身免疫性甲状腺疾病、怀孕、用药和 HIV 阳性。研究人员查阅了 PubMed、Cochrane Library 和 Google Scholar 上 2010 年至 2024 年间发表的文献。关键词包括 "MTHFR"、"基因"、"rs1801133"、"AITD "和 "甲状腺功能减退症"。使用 I² 统计量评估异质性，并相应地应用固定或随机效应模型。结果GA基因型和A等位基因与甲状腺功能减退症风险增加有关（OR = 0.55，95 % CI：0.35-0.89；OR = 0.62，95 % CI：0.40-0.94）。AA 基因型对 MTHFR rs1801133 多态性无明显影响。G 等位基因与甲状腺功能减退症风险降低有关（OR = 0.67，95 % CI：0.47-0.97）。TNFSF4 rs3850641的基因型分布或遗传模型未发现明显影响，而TNFSF4 rs7514229多态性、GT基因型和T等位基因与甲减风险降低有关（OR = 0.46，95 % CI：0.23-0.92；OR = 0.48，95 % CI：0.25-0.94）。显性模型显示，GT+TT 基因型的风险升高；在 MTHFR rs1801133 多态性中，等位基因模型显示与甲状腺功能减退症有显著联系（OR = 1.49，95 % CI：0.99-2.22），而其他基因模型未显示持续的显著相关性。结论研究发现，MTHFR rs1801133 多态性与甲状腺功能减退症风险之间存在很强的相关性，尤其是在 GA 基因型和 A 等位基因中。虽然一些 TNFSF4 多态性与甲状腺功能减退症有关联，但总体影响不大。未来的研究应包括更重要、更多样化的人群，以更好地了解这些遗传风险因素及其对甲减预防和管理的影响。

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来源期刊

Gene Reports Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

3.30

自引率

7.70%

发文量

246

审稿时长

49 days

期刊介绍： Gene Reports publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses. Gene Reports strives to be a very diverse journal and topics in all fields will be considered for publication. Although not limited to the following, some general topics include: DNA Organization, Replication & Evolution -Focus on genomic DNA (chromosomal organization, comparative genomics, DNA replication, DNA repair, mobile DNA, mitochondrial DNA, chloroplast DNA). Expression & Function - Focus on functional RNAs (microRNAs, tRNAs, rRNAs, mRNA splicing, alternative polyadenylation) Regulation - Focus on processes that mediate gene-read out (epigenetics, chromatin, histone code, transcription, translation, protein degradation). Cell Signaling - Focus on mechanisms that control information flow into the nucleus to control gene expression (kinase and phosphatase pathways controlled by extra-cellular ligands, Wnt, Notch, TGFbeta/BMPs, FGFs, IGFs etc.) Profiling of gene expression and genetic variation - Focus on high throughput approaches (e.g., DeepSeq, ChIP-Seq, Affymetrix microarrays, proteomics) that define gene regulatory circuitry, molecular pathways and protein/protein networks. Genetics - Focus on development in model organisms (e.g., mouse, frog, fruit fly, worm), human genetic variation, population genetics, as well as agricultural and veterinary genetics. Molecular Pathology & Regenerative Medicine - Focus on the deregulation of molecular processes in human diseases and mechanisms supporting regeneration of tissues through pluripotent or multipotent stem cells.