Polymorphism of Folate Metabolism Genes among Ethnic Kazakh Women with Preeclampsia in Kazakhstan: A Descriptive Study
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Design and Study Subjects
2.2. Ethical Considerations
2.3. Laboratory Setting
2.4. Genes
2.5. Blood Collection and Genomic DNA Isolation
2.6. Statistical Analysis
3. Results
4. Discussion
Study Strengths and Limitations
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Gene | Main Function | Polymorphism Name | Mutation | Pathologic Mechanism | Authors |
---|---|---|---|---|---|
MTR | MTR encodes the enzyme 5-methyltetrahydrofolate-homocysteine methyltransferase (interchangeable terminology-cobalamin-dependent methionine synthase), catalyzes the final step in methionine biosynthesis | MTR A2756G | The A → G polymorphism at position 2756 in the protein binding region of MTR, which replaces aspartic acid with glycine | Elevated homocysteine concentration | [21,43] |
MTRR | The protein encoded by MTRR regenerates a functional methionine synthase via reductive methylation | MTRR A66G | A66G polymorphism (substitution of A for G at position 66) causes the substitution of isoleucine with methionine at codon 22 of MTRR | MTRR is responsible for the remethylation of homocysteine to methionine via a vitamin B12-dependent path | [21,23,25,43] |
MTHFR | The protein encoded by this gene catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a co-substrate for homocysteine remethylation to methionine | MTHFR C677T | C677T polymorphism is a point mutation at position 677 on the MTHFR gene with the substitution of cysteine to thymine nucleotide at that position, which causes the substitution of alanine to valine (Ala222Val) in the catalytic domain of MTHFR | Thermolabile variant the enzyme with reduced catalytic activity and deleterious effect on plasma homocysteine metabolism, leading to hyperhomocysteinemia and coagulation disorders | [10,21,25,36,43] |
Polymorphism | Temperature and Cycles | Restriction Enzyme | Products Size | Primer Sequences |
---|---|---|---|---|
MTR A2756G | 53 °C, 36 | Nsp I | 151 a | Forward: 5′-GAACTAGAAGACAGAAATTCTCTA-3′ |
MTRR A66G | 60 °C, 35 | Hae III | 189 a | Forward: 5′-GCAAAGGCCATCGCAGAAGACAT-3′ |
MTHFR C677T | 58 °C, 35 | Hinf I | 198 a | Forward: 5′-TGAAGGAGAAGGTGTCTGCGGGA-3′ |
Variables | Genes (N = 4246) | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
MTR, A2756G Polymorphism, N = 2140 (100%) | MTRR, A66G Polymorphism, N = 3082 (100%) * | MTHFR, C677T Polymorphism, N = 4246 (100%) * | ||||||||||
Age groups | A/A | A/G | A/G (mutant) | G/G | G/G | A/A | A/G (mutant) | A/G | G/G | C/C | C/T | C/T (mutant) |
mean, (SD±) | 27.98 (12.05) | 27.82 (11.92) | 29.74 (11.49) | 33.33 (1.53) | 31.18 (5.13) | 29.06 (10.57) | 29.96 (11.14) | 30.35 (29.74) | 30.65 (5.2) | 30.84 (24.32) | 30.91 (27.48) | 33.03 (52.53) |
15–19 | 236 (65.19%) | 126 (34.81%) | 0 | 0 | 1 (0.25%) | 114 (28.71%) | 96 (24.18%) | 186 (46.85%) | 2 (0.45%) | 216 (48.97%) | 180 (40.81%) | 43 (9.75%) |
20–24 | 94 (65.28%) | 44 (30.56%) | 6 (4.17%) | 0 | 7 (4.12%) | 53 (31.18%) | 36 (21.18%) | 74 (43.53%) | 24 (9.8%) | 114 (46.53%) | 83 (33.88%) | 24 (9.8%) |
25–29 | 258 (58.24%) | 165 (37.25%) | 20 (4.51%) | 0 | 29 (4.63%) | 176 (28.12%) | 159 (25.4%) | 262 (41.85%) | 60 (6.9%) | 410 (47.18%) | 328 (37.74%) | 71 (8.17%) |
30–34 | 349 (65.85%) | 156 (29.43%) | 23 (4.34%) | 2 (0.38%) | 25 (2.96%) | 278 (32.9%) | 189 (22.37%) | 353 (41.78%) | 57 (4.73%) | 614 (50.95) | 432 (35.85%) | 102 (8.46%) |
35–39 | 273 (62.19%) | 141 (32.12%) | 24 (5.47%) | 1 (0.23%) | 26 (3.79%) | 194 (28.28%) | 172 (25.07%) | 294 (42.86%) | 50 (5.14%) | 457 (46.97%) | 377 (38.75%) | 89 (9.15%) |
40–44 | 91 (62.76%) | 52 (35.86%) | 2 (1.38%) | 0 | 3 (1.18%) | 49 (19.22%) | 77 (30.2%) | 126 (49.41%) | 7 (1.93%) | 171 (47.24%) | 143 (39.5%) | 41 (11.33%) |
45–49 | 23 (60.53%) | 14 (36.84%) | 1 (2.63%) | 0 | 0 | 14 (22.58%) | 13 (20.97%) | 35 (56.45%) | 0 | 50 (56.18%) | 33 (37.08%) | 6 (6.74%) |
50≤ | 20 (68.97%) | 7 (24.14%) | 2 (6.9%) | 0 | 0 | 7 (17.07%) | 14 (34.15%) | 20 (48.78%) | 0 | 23 (37.1%) | 32 (51.61%) | 7 (11.29%) |
Total | 1344 | 705 | 88 | 3 | 91 | 885 | 756 | 1350 | 200 | 2055 | 1608 | 383 |
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Kaldygulova, L.; Yerdessov, S.; Ukybassova, T.; Kim, Y.; Ayaganov, D.; Gaiday, A. Polymorphism of Folate Metabolism Genes among Ethnic Kazakh Women with Preeclampsia in Kazakhstan: A Descriptive Study. Biology 2024, 13, 648. https://doi.org/10.3390/biology13090648
Kaldygulova L, Yerdessov S, Ukybassova T, Kim Y, Ayaganov D, Gaiday A. Polymorphism of Folate Metabolism Genes among Ethnic Kazakh Women with Preeclampsia in Kazakhstan: A Descriptive Study. Biology. 2024; 13(9):648. https://doi.org/10.3390/biology13090648
Chicago/Turabian StyleKaldygulova, Lyazzat, Sauran Yerdessov, Talshyn Ukybassova, Yevgeniy Kim, Dinmukhamed Ayaganov, and Andrey Gaiday. 2024. "Polymorphism of Folate Metabolism Genes among Ethnic Kazakh Women with Preeclampsia in Kazakhstan: A Descriptive Study" Biology 13, no. 9: 648. https://doi.org/10.3390/biology13090648