Association of three missense mutations in the homocysteine-related MTHFR and MTRR gene with risk of polycystic ovary syndrome in Southern Chinese women

Feng, Wan-Qin; Zhang, Yan; Pan, Yuan; Zhang, Yi; Liu, Minjuan; Huang, Yuxin; Xiao, Yuanling; Mo, Wen-yu; Jiao, Junjie; Wang, Xiaoyang; Tian, Daiyin; Yang, Lixia; Ma, Ying

doi:10.1186/s12958-020-00688-8

Cited by 15 publications

(10 citation statements)

References 43 publications

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“…Future multicenter prospective cohort studies are needed to confirm this conclusion. Third, although many factors that may affect Hcy levels were included in this study, some were not included in the analysis, such as MTHFR gene mutations, which have been found to cause high Hcy levels ( Feng et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Homocysteine Levels Are Associated With the Rupture of Intracranial Aneurysms

Wei

Yuan

et al. 2022

Front. Neurosci.

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BackgroundHomocysteine (Hcy) levels may be associated with the development of intracranial aneurysms (IAs). However, whether it increases the risk of rupture of IAs is unknown. This study aimed to determine the association between homocysteine levels and IA rupture.MethodsWe retrospectively reviewed patients with IAs and subarachnoid hemorrhage (SAH) at our hospital between January 2019 and May 2021. Clinical data, including Hcy levels and IA images, were assessed. The association between Hcy level and IA rupture was investigated using multivariate logistic regression analyses in patients with IAs and SAH.ResultsA total of 589 patients were included. 546 patients with IAs, including 331 UIA (Unruptured IA) and 215 RIA (Ruptured IA). The average age was 57.43 ± 10.86 years old, and 67.03% were women. Among them, all 215 RIAs lead to SAH. In addition, we also enrolled 43 non-aneurysmal subarachnoid hemorrhage (Na-SAH) patients. The average age was 54.12 ± 10.55 years old, and 53.48% were female. After adjusting for confounders in the multivariate model, Hcy levels were correlated with the rupture of IA (odds ratio [OR] 1.069; 95% confidence interval [CI] 1.025–1.114, p = 0.002) and a-SAH (OR 1.083; 95% CI 1.002–1.170, p = 0.046).ConclusionHcy levels were associated with IA rupture. These findings provide novel insights into IAs rupture, and future studies are needed to confirm this relationship.

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Section: Discussionmentioning

confidence: 99%

Homocysteine Levels Are Associated With the Rupture of Intracranial Aneurysms

Wei

Yuan

et al. 2022

Front. Neurosci.

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“…Водночас дані щодо взаємозв'язку між зазначеним поліморфізмом та СПКЯ суперечливі. Так, польські дослідники стверджують, що між генетичною мутацією MTHFR C677Т та СПКЯ відсутня асоціація [13], тоді як науковці з Кореї вважають наявність алеля Т фактором ризику розвитку СПКЯ в корейській попу-ляції [14]. Щодо мутації у локусі 1298 та шансу виникнення СПКЯ довгий час не було жодних доказів.…”

Section: вступunclassified

“…та W. Feng зі співавт. висловлюється припущення, що заміна алеля А на алель С у даному локусі також супроводжується зниженням активності ферменту MTHFR [14,15], однак до кінця це питання залишається не вирішеним.…”

Section: вступunclassified

“…Амінокислотну послідовність ферменту метіонін-синтази-редуктази кодує ген MTRR. При поліморфізмі у цьому гені відбувається заміна амінокислотного залишку ізолейцину на метіонін, а функціональна активність ферменту MTRR зменшується [14]. Зниження активності кожного з ензимів фолатного циклу супроводжується порушенням процесу метилювання, а дефект у роботі донора метильних груп -метіоніну тягне за собою довгий ланцюг генетичних подій, до яких залучені поліморфні алелі та гени, що регулюють метаболізм фолатів і впливають на розвиток ГГЦ.…”

Section: вступunclassified

“…Встановлено, що наявність мутаційного алеля Т супроводжувалась наявністю асоціації із СПКЯ (χ 2 = 0,04; Р = 0,84; OR = 1,19; 95% CI 0,52-2,71), яка зростала зі збільшенням кількості алелів (ТТ) (χ 2 = 3,919; Р = 0,048; OR = 7,69; 95% CI 0,98-59,87). Отримані нами результати узгоджуються з даними інших дослідників та підтверджують припущення, що алель T може бути поєднаний з ризиком виникнення СПКЯ [14]. Наявність мутаційного варіанта гена MTHFR C677T в обстежених пацієнток також поєднувалась зі зростанням концентрації ГЦ у сироватці крові, при цьому даний показник був вірогідно (Р < 0,001) вищим за рівень ГЦ як у здорових жінок, так і у хворих з генотипом С677С.…”

Section: результатиunclassified

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Level of homocysteine and polymorphism of genes involved in folate metabolism in women with polycystic ovary syndrome

Arkhypkina,

Bondarenko,

Lyubimovа

et al. 2023

Mìžnarodnij endokrinologìčnij žurnal

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Background. Polycystic ovary syndrome (PCOS) is a multifactorial disease in the development of which gene polymorphism plays an important role. In recent years, data on the role of homocysteine (Hcy) in the formation of PCOS have appeared, and hyperhomocysteinemia is even considered one of the main symptoms of this disease. The causes of an impaired Hcy metabolism are varied and mainly depend on the condition of the genes encoding enzymes of the folate cycle. At the same time, available data on the effect of the 5,10-methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), and methionine synthase reductase (MTRR) gene polymorphisms on the development of hyperhomocysteinemia and the risk of PCOS are few and contradictory. The purpose of the study was to investigate the polymorphisms of the main genes encoding enzymes of the folate cycle (MTHFR, MTR, MTRR) and to reveal their relationship with the level of Hcy in PCOS. Material and methods. One hundred and twenty-nine women aged 20–28 years were examined: the main group — 98 patients with PCOS, the control group — 31 healthy women. The serum content of Hcy was evaluated and a molecular genetic study was conducted to identify the MTHFR, MTR, and MTRR genes. Results. Polymorphic variants of genes involved in folate metabolism were found in both patients with PCOS and in healthy women. However, serum concentration of Hcy was significantly higher in PCOS. Analysis of the MTHFR C677T polymorphism gene showed that the presence of the mutant T allele was associated with an increased Hcy level (12.9 ± 0.2 μmol/l) and the risk of PCOS (odds ratio (OR) = 1.19; 95% confidence interval (CI) 0.52–2.71). In the presence of two T alleles, the level of Hcy (14.6 ± 0.3 µmol/L) and the risk of developing PCOS (OR = 7.69; 95% CI 0.98–59.87) increased even further compared to the functionally “normal” C677C genotype. There was also an association between the MTHFR gene polymorphism at locus 1298 and PCOS whose strength depended on the number of pathological C alleles and was mediated by Hcy content, although this mutation was accompanied by a less significant increase in the level of Hcy than the mutation at locus 677. Compared to carriers of the homozygous A1298A genotype, the risk of developing PCOS was 5.7 times higher in patients with one C allele, and 7.3 times higher in the presence of two C alleles. The MTRR A66A and A66G genotypes were associated with a significant increase in the level of Hcy compared to that of the control group and were associated with an increased risk of PCOS. The mutant homozygous G66G genotype was more common in the control group and had no significant effect on Hcy concentration. It is not proved that the MTR gene is a candidate gene for the development of PCOS, and its polymorphic variants have a negative effect on the level of Hcy. The combination of MTHFR C677T and A1298C, MTHFR C677T and MTR A2756G, MTR A2756G and MTRR A66G gene mutations are associated with a greater increase in Hcy and the risk of developing PCOS compared to any individual monomutation. Conclusions. The MTHFR gene polymorphism and the synergistic effect of the MTHFR, MTR, MTRR gene mutations can be important genetic determinants for homocysteine levels and the risk of PCOS.

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Significant alteration of protein profiles in a mouse model of polycystic ovary syndrome

Meng,

Yang,

Luo

et al. 2023

Molecular Reproduction Devel

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Polycystic ovary syndrome (PCOS) is an endocrine disorder, affecting women of child‐bearing age, and the incidence rate is growing and assuming epidemic proportions. The etiology of PCOS remains unknown and there is no cure. Some animal models for PCOS have been established which have enhanced our understanding of the underlying mechanisms, but omics data for revealing PCOS pathogenesis and for drug discovery are still lacking. In the present study, proteomics analysis was used to construct a protein profile of the ovaries in a PCOS mouse model. The result showed a clear difference in protein profile between the PCOS and control group, with 495 upregulated proteins and 404 downregulated proteins in the PCOS group. The GO term and KEGG pathway analyses of differentially expressed proteins mainly showed involvement in lipid metabolism, oxidative stress, and immune response, which are consistent with pathological characteristics of PCOS in terms of abnormal metabolism, endocrine disorders, chronic inflammation and imbalance between oxidant and antioxidant levels. Also, we found that inflammatory responses were activated in the PCOS ovarium, while lipid biosynthetic process peroxisome, and bile secretion were inhibited. In addition, we found some alteration in unexpected pathways, such as glyoxylate and dicarboxylate metabolism, which should be investigated. The present study makes an important contribution to the current lack of PCOS ovarian proteomic data and provides an important reference for research and development of effective drugs and treatments for PCOS.

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Association of three missense mutations in the homocysteine-related MTHFR and MTRR gene with risk of polycystic ovary syndrome in Southern Chinese women

Cited by 15 publications

References 43 publications

Homocysteine Levels Are Associated With the Rupture of Intracranial Aneurysms

Homocysteine Levels Are Associated With the Rupture of Intracranial Aneurysms

Level of homocysteine and polymorphism of genes involved in folate metabolism in women with polycystic ovary syndrome

Significant alteration of protein profiles in a mouse model of polycystic ovary syndrome

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