Combined Genotype and Haplotype Distributions of MTHFR C677T and A1298C Polymorphisms: A Cross-sectional Descriptive Study of 13,473 Chinese Adult Women

Overview

Journal Medicine (Baltimore)

Specialty General Medicine

Date 2016 Dec 1

PMID 27902594

Citations 9

Authors

Shujun Fan

Boyi Yang

Xueyuan Zhi

Yanxun Wang

Quanmei Zheng

Guifan Sun

Affiliations

Soon will be listed here.

Abstract

Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms are, independently and/or in combination, associated with many disorders. However, data on the combined genotype and haplotype distributions of the 2 polymorphisms in Chinese population were limited.We recruited 13,473 adult women from 9 Chinese provinces, collected buccal cell samples, and determined genotypes, to estimate the combined genotype and haplotype distributions of the MTHFR C677T and A1298C polymorphisms.In the total sample, the 6 common combined genotypes were CT/AA (29.5%), TT/AA (21.9%), CC/AA (15.4%), CC/AC (14.9%), CT/AC (13.7%), and CC/CC (3.4%); the 3 frequent haplotypes were 677T-1298A (43.6%), 677C-1298A (37.9%), and 677C-1298C (17.6%). Importantly, we observed that there were 51 (0.4%) individuals with the CT/CC genotype, 92 (0.7%) with the TT/AC genotype, 17 (0.1%) with the TT/CC genotype, and that the frequency of the 677T-1298C haplotype was 0.9%. In addition, the prevalence of some combined genotypes and haplotypes varied among populations residing in different areas and even showed apparent geographical gradients. Further linkage disequilibrium analysis showed that the D' and r values were 0.883 and 0.143, respectively.In summary, the findings of our study provide further strong evidence that the MTHFR C677T and A1298C polymorphisms are usually in trans and occasionally in cis configurations. The frequencies of mutant genotype combinations were relatively higher in Chinese population than other populations, and showed geographical variations. These baseline data would be useful for future related studies and for developing health management programs.

Citing Articles

Folate-Methionine Cycle Disruptions in ASD Patients and Possible Interventions: A Systematic Review.

Roufael M, Bitar T, Sacre Y, Andres C, Hleihel W Genes (Basel). 2023; 14(3).

PMID: 36980981 PMC: 10048251. DOI: 10.3390/genes14030709.

c.665C>T and c.1298A>C Polymorphisms in Tailoring Personalized Anti-TNF-α Therapy for Rheumatoid Arthritis.

Ravaei A, Pulsatelli L, Assirelli E, Ciaffi J, Meliconi R, Salvarani C Int J Mol Sci. 2023; 24(4).

PMID: 36835522 PMC: 9962934. DOI: 10.3390/ijms24044110.

Genetics and Epigenetics of One-Carbon Metabolism Pathway in Autism Spectrum Disorder: A Sex-Specific Brain Epigenome?.

Tisato V, Silva J, Longo G, Gallo I, Singh A, Milani D Genes (Basel). 2021; 12(5).

PMID: 34065323 PMC: 8161134. DOI: 10.3390/genes12050782.

Folate Insufficiency Due to MTHFR Deficiency Is Bypassed by 5-Methyltetrahydrofolate.

Vidmar Golja M, Smid A, Kuzelicki N, Trontelj J, Gersak K, Mlinaric-Rascan I J Clin Med. 2020; 9(9).

PMID: 32887268 PMC: 7564482. DOI: 10.3390/jcm9092836.

Methylenetetrahydrofolate Reductase Gene Variants Confer Potential Vulnerability to Autism Spectrum Disorder in a Saudi Community.

Arab A, Elhawary N Neuropsychiatr Dis Treat. 2020; 15:3569-3581.

PMID: 31920317 PMC: 6938732. DOI: 10.2147/NDT.S230348.

References

Esfahani S, Cogger E, Caudill M . Heterogeneity in the prevalence of methylenetetrahydrofolate reductase gene polymorphisms in women of different ethnic groups. J Am Diet Assoc. 2003; 103(2):200-7. DOI: 10.1053/jada.2003.50030. View

Dekou V, Whincup P, Papacosta O, Ebrahim S, Lennon L, Ueland P . The effect of the C677T and A1298C polymorphisms in the methylenetetrahydrofolate reductase gene on homocysteine levels in elderly men and women from the British regional heart study. Atherosclerosis. 2001; 154(3):659-66. DOI: 10.1016/s0021-9150(00)00522-0. View

Zhong S, Chen Z, Yu X, Li W, Tang J, Zhao J . A meta-analysis of genotypes and haplotypes of methylenetetrahydrofolate reductase gene polymorphisms in breast cancer. Mol Biol Rep. 2014; 41(9):5775-85. DOI: 10.1007/s11033-014-3450-9. View

Cen H, Huang H, Zhang L, Liu L, Zhou L, Xin X . Associations of methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms with genetic susceptibility to rheumatoid arthritis: a meta-analysis. Clin Rheumatol. 2016; 36(2):287-297. DOI: 10.1007/s10067-016-3348-0. View

Pepe G, Vanegas O, Giusti B, Brunelli T, Marcucci R, Attanasio M . Heterogeneity in world distribution of the thermolabile C677T mutation in 5,10-methylenetetrahydrofolate reductase. Am J Hum Genet. 1998; 63(3):917-20. PMC: 1377403. DOI: 10.1086/302015. View

Mansoor A, Mazhar K, Ali L, Muazzam A, Siddiqi S, Usman S . Prevalence of the C677T single-nucleotide polymorphism in the methylenetetrahydrofolate reductase gene among Pakistani ethnic groups. Genet Test Mol Biomarkers. 2009; 13(4):521-6. DOI: 10.1089/gtmb.2009.0012. View

van der Put N, Gabreels F, STEVENS E, Smeitink J, Trijbels F, Eskes T . A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects?. Am J Hum Genet. 1998; 62(5):1044-51. PMC: 1377082. DOI: 10.1086/301825. View

Hanson N, Aras O, Yang F, Tsai M . C677T and A1298C polymorphisms of the methylenetetrahydrofolate reductase gene: incidence and effect of combined genotypes on plasma fasting and post-methionine load homocysteine in vascular disease. Clin Chem. 2001; 47(4):661-6. View

Xie S, Liu Z, Yu J, Liu L, Wang W, Xie D . Association between the MTHFR C677T polymorphism and risk of cancer: evidence from 446 case-control studies. Tumour Biol. 2015; 36(11):8953-72. DOI: 10.1007/s13277-015-3648-z. View

10.

Wilcken B, Bamforth F, Li Z, Zhu H, Ritvanen A, Renlund M . Geographical and ethnic variation of the 677C>T allele of 5,10 methylenetetrahydrofolate reductase (MTHFR): findings from over 7000 newborns from 16 areas world wide. J Med Genet. 2003; 40(8):619-25. PMC: 1735571. DOI: 10.1136/jmg.40.8.619. View

11.

Li Z, Ren A, Zhang L, Ye R, Li S, Zheng J . Extremely high prevalence of neural tube defects in a 4-county area in Shanxi Province, China. Birth Defects Res A Clin Mol Teratol. 2006; 76(4):237-40. DOI: 10.1002/bdra.20248. View

12.

Yang B, Fan S, Zhi X, Li Y, Liu Y, Wang D . Associations of MTHFR gene polymorphisms with hypertension and hypertension in pregnancy: a meta-analysis from 114 studies with 15411 cases and 21970 controls. PLoS One. 2014; 9(2):e87497. PMC: 3914818. DOI: 10.1371/journal.pone.0087497. View

13.

Jacques P, Bostom A, Williams R, Ellison R, Eckfeldt J, Rosenberg I . Relation between folate status, a common mutation in methylenetetrahydrofolate reductase, and plasma homocysteine concentrations. Circulation. 1996; 93(1):7-9. DOI: 10.1161/01.cir.93.1.7. View

14.

Zhu X, Liu Z, Yan S, Wang W, Chang R, Zhang C . Association between the MTHFR A1298C polymorphism and risk of cancer: evidence from 265 case-control studies. Mol Genet Genomics. 2015; 291(1):51-63. DOI: 10.1007/s00438-015-1082-y. View

15.

Weiner A, Boyarskikh U, Voronina E, Mishukova O, Filipenko M . Methylenetetrahydrofolate reductase C677T and methionine synthase A2756G polymorphisms influence on leukocyte genomic DNA methylation level. Gene. 2013; 533(1):168-72. DOI: 10.1016/j.gene.2013.09.098. View

16.

Dong M, Peng B, Lin X, Zhao J, Zhou Y, Wang R . The prevalence of dementia in the People's Republic of China: a systematic analysis of 1980-2004 studies. Age Ageing. 2007; 36(6):619-24. DOI: 10.1093/ageing/afm128. View

17.

Lv Q, Lu J, Sun H, Zhang J . Association of methylenetetrahydrofolate reductase (MTHFR) gene polymorphism with ischemic stroke in the Eastern Chinese Han population. Genet Mol Res. 2015; 14(2):4161-8. DOI: 10.4238/2015.April.27.31. View

18.

Ogino S, Wilson R . Genotype and haplotype distributions of MTHFR677C>T and 1298A>C single nucleotide polymorphisms: a meta-analysis. J Hum Genet. 2003; 48(1):1-7. DOI: 10.1007/s100380300000. View

19.

Stegmann K, Ziegler A, Ngo E, Kohlschmidt N, Schroter B, Ermert A . Linkage disequilibrium of MTHFR genotypes 677C/T-1298A/C in the German population and association studies in probands with neural tube defects(NTD). Am J Med Genet. 1999; 87(1):23-9. View

20.

Liew S, Das Gupta E . Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism: epidemiology, metabolism and the associated diseases. Eur J Med Genet. 2014; 58(1):1-10. DOI: 10.1016/j.ejmg.2014.10.004. View