Alteration of homocysteine catabolism in pre-eclampsia, HELLP syndrome and placental insufficiency.
Hyperhomocysteinemia is a risk factor in obstetrical complications such as pre-eclampsia, 'hemolysis, elevated liver enzymes, low platelet' (HELLP)-syndrome and placental insufficiency. The aim of our study was to investigate the alterations of homocysteine catabolism in these patients in relation to serum B-vitamins and renal function. Maternal fasting serum from pre-eclampsia (n=24), HELLP (n=20) and placental insufficiency (n=25) patients at the time of diagnosis and pregnant controls (n=34) was analyzed for homocysteine and its metabolites cystathionine and methylmalonic acid, the vitamins B6, B12 and folate, renal and additional parameters. Cystathionine, a parameter of homocysteine catabolism, was significantly increased in pre-eclampsia and HELLP compared with controls and placental insufficiency patients (mean concentrations: 343, 324, 248, 227 nmol/l; p=0.001). Homocysteine, folic acid, vitamin B6 and methylmalonic acid, however, did not differ significantly between groups. The main determinants of cystathionine are cystatin C and vitamin B6, whereas the main determinants of homocysteine are folate and uric acid. The strongest dependency of cystathionine on vitamin B6 was observed in pre-eclampsia and HELLP patients. The results suggest that the vitamin B6-dependent trans-sulfuration pathway is activated in pre-eclampsia and HELLP syndrome, probably by oxidative stress. Therefore, the demand for vitamin B6 is increased in these patients. Furthermore, renal dysfunction and low vitamin B6 levels contribute to the increase of cystathionine in pre-eclampsia and HELLP patients.
Herrmann
Wolfgang
W
Department of Clinical Chemistry/Central Laboratory, University Hospital of the Saarland, Homburg, Germany. kchwher@uniklinik-saarland.de
Hübner
Ulrich
U
Koch
Ines
I
Obeid
Rima
R
Retzke
Ulrich
U
Geisel
Jürgen
J
D003540:Cystathionine / Q000097:blood; D055316:Cystatin C; D015891:Cystatins / Q000097:blood; D005260:Female; D005492:Folic Acid / Q000097:blood; D017359:HELLP Syndrome / Q000150:complications / Q000378:metabolism*; D006710:Homocysteine / Q000097:blood / Q000378:metabolism*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000209:etiology / Q000378:metabolism; D007677:Kidney Function Tests; D008764:Methylmalonic Acid / Q000097:blood; D018384:Oxidative Stress / Q000502:physiology; D010927:Placental Insufficiency / Q000150:complications / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000150:complications / Q000378:metabolism*; D011247:Pregnancy; D012720:Severity of Illness Index; D014527:Uric Acid / Q000097:blood; D014805:Vitamin B 12 / Q000097:blood; D025101:Vitamin B 6 / Q000097:blood
C525030:CST3 protein, human; D055316:Cystatin C; D015891:Cystatins; D006710:Homocysteine; D014527:Uric Acid; D003540:Cystathionine; D025101:Vitamin B 6; D008764:Methylmalonic Acid; D005492:Folic Acid; D014805:Vitamin B 12