DOI: 10./gp/59559 Ginekol Pol. 015, 86, Coexistence of the 6C>T and 198A>C MTHFR polymorphisms and its significance in the population of Polish women Znaczenie współwystępowania polimorfizmów 6C>T oraz 198A>C genu MTHFR u kobiet w populacji polskiej 1 Division of Perinatology and Women s Diseases, Poznan University of Medical Sciences, Poland Division of Gynecology and Obstetrics, Podhale Multidisciplinary Hospital, Nowy Targ, Poland Laboratory of Molecular Biology in the Division of Perinatology and Women s Diseases, Poznan University of Medical Sciences, Poznan, Poland Student Scientific Association of Department of Gynecological Endocrinology, Poznan University of Medical Sciences, Poland Abstract Objectives: The aim of the study was to evaluate the frequency of the 6C>T and 198A>C polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene, as well as the coexistence of both these genetic variants in women from the Polish population. Material and methods: A total of 66 women from the Polish population were enrolled in the study group. The frequency of the investigated genotypes of the 6C>T and 198A>C polymorphisms of the MTHFR gene was analyzed with the use of PCR/RFLP methods. Results: The frequency of the 6CC, 6CT and 6TT genotypes in the studied population of women was 50.60%, 9.88% and 9.5%, respectively. As to the 198AA, 198AC and 198CC genotypes, the obtained results were as follows:.5%,.88% and 9.%, respectively (Tables II and III). Simultaneous analysis revealed the most frequent coexistence of 6CC/198AC (8.85%), 6CT/198AA (0.85%) and 6CT/198AC (19.0%) genotypes. The coexistence of 6CC/198AA (1.9%), 6CC/198CC (9.%) and 6TT/198AA (9.51%) genotypes was observed less frequently. In the studied population of Polish women, the coexistence of 6CT/198CC, 6TT/198AC and 6TT/198CC genotypes has been not observed. Conclusions: The frequency and coexistence of genotypes of the 6C>T and 198A>C MTHFR gene polymorphisms in the studied population of Polish women is similar to other NorthEuropean populations. Women carriers of the mutated variants of both, 6C>T and 198A>C polymorphisms of the MTHFR gene should receive special perinatal care in order to prevent fetal defects and thrombosisrelated complications during pregnancy. It is vital to emphasize the significance of proper education of folate supplementation, especially in pregnant patients and women of reproductive age. Key words: MTHFR / / / Corresponding author: Hubert Wolski Division of Perinatology and Women s Disease Poznan University of Medical Sciences Tel. 61819, fax. 61856 email: hubertwolski@wp.pl Otrzymano: 0.0.015 Zaakceptowano do druku: 01.0.015 Polskie Towarzystwo Ginekologiczne Nr 10/015
Ginekol Pol. 015, 86, DOI: 10./gp/59559 Hubert Wolski et al. Coexistence of the 6C>T and 198A>C MTHFR polymorphisms and its significance in the population of Polish women. Streszczenie Cel: Określenie częstości występowania polimorfizmów 6C>T i 198A>C genu kodującego reduktazę metylenotetrahydrofolianową (MTHFR) oraz ocena współwystępowania obydwu wariantów genetycznych u kobiet w populacji polskiej. Materiał i metoda: Do grupy badawczej włączono 66 kobiety z populacji polskiej. Częstość występowania genotypów polimorfizmów 6C>T oraz 198A>C genu MTHFR została zbadana metodą PCR/RFLP. Wyniki: W badanej grupie częstość występowania genotypów 6CC, 6CT oraz 6TT wynosiła odpowiednio 50,60%, 9,88% oraz 9,5%. Natomiast genotypy 198AA, 198AC oraz 198CC występowały z częstością,5%,,88% oraz 9,%. Jednocześnie analiza współwystępowania genotypów pozwoliła na określenie najczęściej występujących genotypów 6CC/198AC (8,85%), 6CT/198AA (0,85%), 6CT/198AC (19,0%). Współwystępowanie genotypów 6CC/198AA (1,9%), 6CC/198CC (9,%), 6TT/198AA (9,51%) było obserwowane rzadziej. W badanej populacji nie zaobserwowano współwystępowania polimorfizmów 6CT/198CC, 6TT/198AC, 6TT/198CC. Wnioski: Częstość występowania i współwystępowania polimorfizmów 6C>T i 198A>C u kobiet w populacji polskiej jest porównywalna do częstości występowania tych wariantów w innych populacjach północnoeuropejskich. Kobiety, nosicielki zmutowanych genotypów polimorfizmów 6C>T i 198A>C genu kodującego MTHFR, powinny zostać objęte specjalną opieką perinatalną, z powodu wzrostu ryzyka wystąpienia wad płodu oraz powikłań zakrzepowych w czasie ciąży. Należy zwrócić uwagę na właściwą edukację i suplementację folianami kobiet, szczególnie w wieku rozrodczym oraz w czasie ciąży. Słowa kluczowe: MTHFR / / / Introduction MTHFR 6C>T 198A>C 6C>T 6TT 198A>C 6C>T 198A>C 6TT 198CC 198C 6CT/198AC 6TT/198AA 6TT/198AA 6CT/198AC MTHFR 6C>T 198A>G MTHFR Objectives 6C>T 198A>C MTHFR Material and methods Study group Nr 10/015 Polskie Towarzystwo Ginekologiczne
DOI: 10./gp/59559 Ginekol Pol. 015, 86, Hubert Wolski et al. Coexistence of the 6C>T and 198A>C MTHFR polymorphisms and its significance in the population of Polish women. Table I. MTHFR activity [%] according to the presence of 6C>T and 198A>C polymorphisms [Put, Weisberg]. 198A>C MTHFR Genotypes 6C>T MTHFR CC (%) CT (%) TT (%) AA (%) 100 600 00 AC (%) 080 5060 CC (%) 5060 Table II. The frequency of genotypes and alleles of 6C>T MTHFR gene polymorphism. Polymorphism Genotypes Observed value (%) Expected value (%) CC 5 (50.60) 9.6 CT 6 (9.88) 1.56 TT 6 (9.5) 8.68 MTHFR 6C>T Total 66 (100.00) 100.00 Alleles C 9 (0.5) T 90 (9.6) Total 1 (100.00) Table III. The frequency of genotypes and alleles of 198A>C MTHFR gene polymorphism. Polymorphism Genotypes Observed value (%) Expected value (%) AA 8 (.5).8 AC (.88). CC 6 (9.) 11.09 MTHFR 198 A>C Total 66 (100.00) 100.00 Alleles A 88 (66.69) C 1 (.1) Total 1 (100.00) Table IV. The frequency of coexistence of 6C>T and 198A>C polymorphisms. 198A>C MTHFR 6C>T MTHFR CC CT TT Total AA 8 (1.9) 18 (0.85) 6 (9.51) 8 (.5) AC 191 (8.85) 16 (19.0) 0 (0.00) (.88) CC 6 (9.) 0 (0.00) 0 (0.00) 6 (9.) Total 5 (50.61) 6 (9.88) 6 (9.51) 66 (100.00) Genetic analysis 6C>T 198A>C 6C>T 198A>C Hinf Mbo 6CC 6CT 6TT AA AC CC Polskie Towarzystwo Ginekologiczne Nr 10/015
Ginekol Pol. 015, 86, DOI: 10./gp/59559 Hubert Wolski et al. Coexistence of the 6C>T and 198A>C MTHFR polymorphisms and its significance in the population of Polish women. Table V. Coexistence of 6C>T and 198A>C polymorphisms in different populations. Author Population Study group Isotalo i wsp., 000 van der Put i wsp., 1998 De Re i wsp., 010 Kumar Rai i wsp., 005 Rady i wsp, 1999 Sazci i wsp., 005 Bodurogulu i wsp., 005 Ergul i wsp., 00 Canadian newborns 119 Dutch women/men 0 Italian n women/men 5 men 15 women 19 Hindu women 159 Ashkenazi/ Caucasian women/men 186 women/men 18 Turkish women/men 168 Turkish children 9 fathers mothers 80 Turkish women 19 MTHFR 6C>T/MTHFR 198A>C N (%) CC/AA CC/AC CC/CC CT/AA CT/AC CT/CC TT/AA TT/AC TT/CC (1.0) 6 (15.0) (5.0) 19 (60) 5 (.60) (0.80) (.0) 1 (8.10) 8 (10.60) 11 (11.80) (.0) (5.00) 5 (18.10) (5.0) 105 (6.10) 90 (19.80) 58 (18.0) (.00) 59 (.10) 50 (6.90) (15.50) 01 (.80) 1 (1.00) 10 (1.90) (1.5) 5 (.0) 9 (.60) 8 (9.0) 8 (8.0) (.0) 15 (10.80) (1.80) 0 (10.80) 1 (8.10) 16 (8.0) (.50) 10 (1.90) (5.00) 1 (.0) 1 (11.0) 81 (0.10) 98 (1.60) 0 (.0) 8 (0.10) 1 (1.0) 19 (10.0) 9 (19.60) 11 (.0) 8 (0.10) 8 (8.90) (1.5) 8 (.90) (19.0) 81 (0.10) (0.0) 95 (0.0) (0.0) 1 (8.80) 9 (1.00) (.0) 6 (1.60) 6 (8.00) (.50) (8.5) 5 (18.10) (0.0) 1 (0.0) (1.0) (.50) (1.00) (.10) 1 (10.10) 6 (9.00) 5 (1.60) (1.00) 1 (9.0) (1.0) 5 (1.0) 9 (6.0) 16 (8.0) 8 (8.60) (.80) (8.5) (.60) (1.0) (1.5) 5 (1.60) (1.0) (1.90) 1 (0.60) (1.00) 5 (.60) Results 6CC 6CT 6TT 198AA, 198AC 198CC 6CC/198AC 6CT/198AA 6CT/198AC 6CC/198AA 6CC/198CC 6TT/198AA 6CT/198CC 6TT/198AC 6TT/198CC Discussion 6C>T 198A>C MTHFR 6TT/198AA 6CT/198AC 6TT/198AA 6CC/198CC 6CT/198AA 6CT/198CC 6TT/198AC 6TT/198CC 6CT/198AC 6TT/18AA MTHFR 6CT/198AC Nr 10/015 Polskie Towarzystwo Ginekologiczne 5
DOI: 10./gp/59559 Ginekol Pol. 015, 86, Hubert Wolski et al. Coexistence of the 6C>T and 198A>C MTHFR polymorphisms and its significance in the population of Polish women. 6CT/198AC 6CT/198AC 6CC/198AC 6TT/198CC 6CC/198AC 6CT/198AA 6TT/198AA 6TT/198CC 6CT/198CC 6TT/198AC 6CT/198CC 6TT/198AC 6CT/198CC 6TT/198AC 6C>T 198A>C MTHFR 6CT/198AC 6CT/198CC 6TT/198AC MTHFR 6T 6T 6T 6C>T 6C>T 6TMTHFR 6CC 6TMTHFR 6T MTHFR MTHFR 6C>T 198A>C 6TT, 198CC, 6CT/198AC 6TT/198AA Conclusions 6C>T 198A>C MTHFR 6C>T 198A>C MTHFR Oświadczenie autorów 1. Hubert Wolski autor koncepcji i założeń pracy, przygotowanie anuskryptu i piśmiennictwa, ostateczna korekta i akceptacja manuskryptu autor zgłaszający i odpowiedzialny za manuskrypt.. Maria Kocięska zebranie materiału, analiza statystyczna wyników, przygotowanie manuskryptu.. Aleksandra E. Mrozikiewicz współautor tekstu pracy, korekta i aktualizacja literatury. Magdalena Barlik analiza i interpretacji wyników, współautor tekstu pracy. 5. Grażyna Kurzawińska współautor tekstu pracy, analiza statystyczna wyników. Źródło finansowania: badania statutowe Kliniki Perinatologii i Chorób Kobiecych UM w Poznaniu nr: 5001018000 Konflikt interesów: Autorzy nie zgłaszają konfliktu interesów oraz nie otrzymali żadnego wynagrodzenia związanego z powstawaniem pracy 6 Polskie Towarzystwo Ginekologiczne Nr 10/015
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