Methylenetetrahydrofolate Reductase Polymorphism
Affects the Change in Homocysteine and Folate Concentrations Resulting from Low
Dose Folic Acid Supplementation in Women with Unexplained Recurrent
Miscarriages
- Willianne L.D.M. Nelen3,
- Henk J. Blom*,
- Chris M. G. Thomas,
- Eric A. P. Steegers,,
- Godfried H. J. Boers
- Tom K.A.B. Eskes
+
Author Affiliations
- Department of Obstetrics and Gynecology, *
- Pediatrics and †Internal Medicine, University Hospital Nijmegen St Radboud, 6500 HB Nijmegen, The Netherlands
Abstract
To determine the effects of daily supplementation of 0.5 mg
folic acid on homocysteine and folate concentrations, we investigated 49 women
with a history of unexplained recurrent miscarriages. A methionine loading test
(including the vitamin concentrations of concern) was used preceding and after
2 mo of folic acid intake. Subsequently, these effects were studied after
stratification for C677T 5,10-methylenetetrahydrofolate reductase (MTHFR)
polymorphism. Folic acid supplementation (for 2 mo) reduced the median fasting
and delta (after-load minus fasting) total plasma homocysteine (tHcy)
concentrations 27% (P < 0.001) and 14% (P < 0.05),
respectively. Median serum and red cell folate concentrations increased 275 and
70%, respectively (P < 0.01). The homocysteine-lowering effect was
most marked in women with the highest tHcy concentrations at baseline. All
MTHFR-genotypes (homozygous T/T, n = 8; heterozygous T/C, n = 23;
wild type C/C, n = 18) had a different response to the supplementation.
After 2 mo, homozygous women showed the greatest decline in median fasting
(−41%; P < 0.01) tHcy concentrations, but the lowest absolute
increase in serum folate concentration (+26 nmol/L; P < 0.05). In
conclusion, 2 mo of daily supplementation of 0.5 mg folic acid in women with a
history of unexplained recurrent miscarriages caused, in general, substantially
reduced tHcy concentrations. This effect was most distinct in women with the
highest tHcy concentrations at baseline and in women homozygous for the 677 C→T
mutation of the MTHFR-gene.
1.Willianne L.D.M. Nelen3,
2.Henk J. Blom ,
3.Chris M. G. Thomas,
4.Eric A. P. Steegers,,
5.Godfried H. J. Boer
6.Tom K.A.B. Eskes
+ Afiliasi Penulis
Departemen Obstetri dan Ginekologi, *
Pediatrics dan † Internal Medicine, University Hospital Nijmegen St Radboud, 6500 HB Nijmegen, Belanda
Abstrak
Untuk menentukan efek dari suplementasi harian 0,5 mg asam folat pada homocysteine dan konsentrasi folat, kami meneliti 49 wanita dengan riwayat keguguran berulang dijelaskan. Sebuah uji pembebanan metionin (termasuk konsentrasi vitamin perhatian) digunakan sebelumnya dan setelah 2 mo asupan asam folat. Selanjutnya, efek ini dipelajari setelah stratifikasi untuk C677T 5,10-methylenetetrahydrofolate reduktase (MTHFR) polimorfisme. Suplementasi asam folat (untuk 2 bulan) mengurangi median puasa dan delta (setelah dikurangi beban-puasa) homosistein Total (tHcy) konsentrasi plasma 27% (P <0,001) dan 14% (P <0,05), masing-masing. Konsentrasi folat sel Median serum dan merah meningkat 275 dan 70%, masing-masing (P <0,01). Efek homosistein penurun yang paling ditandai pada wanita dengan konsentrasi tHcy tertinggi pada awal. Semua MTHFR-genotipe (homozigot T / T, n = 8; heterozigot T / C, n = 23; wild type C / C, n = 18) memiliki respon yang berbeda untuk suplementasi. Setelah 2 mo, wanita homozigot menunjukkan penurunan terbesar dalam puasa median (-41%, P <0,01) konsentrasi tHcy, namun peningkatan mutlak terendah pada konsentrasi folat serum (+26 nmol / L, P <0,05). Sebagai kesimpulan, 2 mo suplementasi harian 0,5 mg asam folat pada wanita dengan riwayat keguguran berulang dijelaskan disebabkan, secara umum, konsentrasi tHcy substansial berkurang. Efek ini adalah yang paling berbeda pada wanita dengan konsentrasi tHcy tertinggi pada awal dan pada wanita homozigot untuk 677 C → T mutasi MTHFR-gen.
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