Association of polymorphism of methylene-tetrahydro-folate-reductase with urinary albumin excretion rate in type 1 diabetes mellitus but not with preeclampsia, retinopathy, and preterm delivery.
OBJECTIVE
The genetic setting is a potential risk factor for dysfunction of vascular endothelial cells. The prevalence of polymorphism in the methylene-tetrahydro-folate-reductase (MTHFR) gene (677C-->T) was evaluated in diabetic pregnancy complicated by preeclampsia, nephropathy, retinopathy, and preterm delivery. The role of hyperhomocysteinemia in microangiopathy in diabetes mellitus has been debated and is mainly seen with reduced activity of the MTHFR gene. A polymorphism in the gene for MTHFR is identified causing this phenomenon.


METHODS
Two hundred and sixty-eight pregnant women with type 1 diabetes mellitus were recruited. Two hundred and thirty-three women were successfully analyzed for MTHFR gene polymorphism 677C-->T and compared to the incidence of the polymorphism in the background population (n=1084). The pregnancy data charts were reviewed retrospectively.


RESULTS
The frequency of the MTHFR polymorphism in the background population was 29% and the heterozygozity 42%. The women with type 1 diabetes mellitus had a higher frequency of the MTHFR polymorphism with 52% heterozygotes and 9% homozygotes than had the background population (heterozygotes, background vs. type 1 diabetes mellitus: chi(2)=14, df=1, p<0.0002). The odds ratio for heterozygozity of the MTHFR polymorphism was 1.8 (95% Cl: 1.3-2.4) in women with type 1 diabetes mellitus. Women with either micro- or macroalbuminuria had a higher frequency of MTHFR polymorphism with 61% heterozygotes and 3% homozygotes than had the background population (heterozygotes: chi(2)=8.9, df=1, p<0.01). The odds ratio for heterozygozity of the MTHFR polymorphism was 2.3 (95% CI: 1.4-4) in women with type 1 diabetes mellitus.


CONCLUSIONS
An association was demonstrated between the MTHFR polymorphism and type 1 diabetes mellitus as well as increasing albumin excretion rate in pregnant women.
Lauszus
F F
FF
Gynecological/Obstetrical Department, Skejby Hospital, Aarhus, Denmark. affl@ringamt.dk
Grøn
P L
PL
Klebe
J G
JG
D000419:Albuminuria / Q000150:complications; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000235:genetics*; D003930:Diabetic Retinopathy / Q000150:complications; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D007752:Obstetric Labor, Premature / Q000150:complications*; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*; D011110:Polymorphism, Genetic; D011225:Pre-Eclampsia / Q000150:complications*; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000150:complications* / Q000235:genetics*; D012189:Retrospective Studies; D012307:Risk Factors
D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)