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Reference ranges and determinants of  S-adenosylmethionine and S-adenosylhomocysteine   R. de Jonge, R. de Nooijer, H. van Lenthe, B. van Zelst, M. Duran, W. Kulik , J. Lindemans  1 Dept. of Clinical Chemistry,  Erasmus  MC Rotterdam,  and  2 Laboratory Genetic Metabolic Diseases, Depts. of Clinical Chemistry and Pediatrics, Emma Childrens Hospital, University of Amsterdam, Academic Medical Center, Amsterdam; NL Introduction The pathophysiology behind the association between hyperhomocysteinemia and (cardiovascular) disease might be better explained by increased S-adenosylhomocysteine (SAH) and a decreased S-adenosylmethionine (SAM)/SAH ratio, reflecting cellular hypomethylation (Figure 1). We determined reference ranges for fasting SAM, SAH, and SAM/SAH and investigated determinants of these levels.   Furthermore, fasting SAH was higher ( P =0.02) and SAM/SAH was lower ( P =0.01) in female patients compared to healthy women (Figure 2) Figure 2: SAM/SAH in female patients vs. controls B-vitamin levels were unrelated to plasma SAM, SAH and SAM/SAH levels.  MTHFR  677 TT was associated with increased fasting SAM ( P =0.08) and fasting SAH ( P =0.008) and decreased fasting SAM/SAH ( P =0.07).  Table 2: Univariate regression fasting SAM/SAH Conclusions Gender differences exist for SAM, SAH and SAM/SAH .  Patients with a history of pre-eclampsia show increseased SAH levels and decreased SAM/SAH ratios, possibly reflecting cellular hypomethylation. The  MTHFR  677C>T polymorphism was related to SAM and SAH whereas B-vitamins were not. This may have implications for the efficacy of vitamin intervention trials aimed at reducing homocysteine and cardiovascular risk. Figure 1: Homocysteine and SAM/SAH metabolism Methods We took non-fasting blood of 100 (50 male, 50 female) healthy Caucasian blood bank donors. Furthermore, fasting and post-methionine (0.1 g/kg) blood samples of patients with a history of pre-eclampsia (n=44) were analysed for SAM and SAH (LC-MS/MS), homocysteine and vitamin B6 (HPLC), and folate and vitamin B12 ( Roche E170 analyzer). Polymorphisms in folate-related genes were  detected by PCR-RFLP. Results In healthy Caucasians (mean age 48 ? 12 years), SAM (95% central range: male: 80-214 nmol/L; female: 66-128 nmol/L) and SAH (male: 15-31 nmol/L; female: 10-23 nmol/L) were significantly lower in females whereas the SAM/SAH ratio was higher (male: 3.3-8.2; female: 3.8-8.8; see Table 1).   Table 1: Reference ranges SAM and SAH
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Poster SAM/SAH

  • 1. Reference ranges and determinants of S-adenosylmethionine and S-adenosylhomocysteine R. de Jonge, R. de Nooijer, H. van Lenthe, B. van Zelst, M. Duran, W. Kulik , J. Lindemans 1 Dept. of Clinical Chemistry, Erasmus MC Rotterdam, and 2 Laboratory Genetic Metabolic Diseases, Depts. of Clinical Chemistry and Pediatrics, Emma Childrens Hospital, University of Amsterdam, Academic Medical Center, Amsterdam; NL Introduction The pathophysiology behind the association between hyperhomocysteinemia and (cardiovascular) disease might be better explained by increased S-adenosylhomocysteine (SAH) and a decreased S-adenosylmethionine (SAM)/SAH ratio, reflecting cellular hypomethylation (Figure 1). We determined reference ranges for fasting SAM, SAH, and SAM/SAH and investigated determinants of these levels. Furthermore, fasting SAH was higher ( P =0.02) and SAM/SAH was lower ( P =0.01) in female patients compared to healthy women (Figure 2) Figure 2: SAM/SAH in female patients vs. controls B-vitamin levels were unrelated to plasma SAM, SAH and SAM/SAH levels. MTHFR 677 TT was associated with increased fasting SAM ( P =0.08) and fasting SAH ( P =0.008) and decreased fasting SAM/SAH ( P =0.07). Table 2: Univariate regression fasting SAM/SAH Conclusions Gender differences exist for SAM, SAH and SAM/SAH . Patients with a history of pre-eclampsia show increseased SAH levels and decreased SAM/SAH ratios, possibly reflecting cellular hypomethylation. The MTHFR 677C>T polymorphism was related to SAM and SAH whereas B-vitamins were not. This may have implications for the efficacy of vitamin intervention trials aimed at reducing homocysteine and cardiovascular risk. Figure 1: Homocysteine and SAM/SAH metabolism Methods We took non-fasting blood of 100 (50 male, 50 female) healthy Caucasian blood bank donors. Furthermore, fasting and post-methionine (0.1 g/kg) blood samples of patients with a history of pre-eclampsia (n=44) were analysed for SAM and SAH (LC-MS/MS), homocysteine and vitamin B6 (HPLC), and folate and vitamin B12 ( Roche E170 analyzer). Polymorphisms in folate-related genes were detected by PCR-RFLP. Results In healthy Caucasians (mean age 48 ? 12 years), SAM (95% central range: male: 80-214 nmol/L; female: 66-128 nmol/L) and SAH (male: 15-31 nmol/L; female: 10-23 nmol/L) were significantly lower in females whereas the SAM/SAH ratio was higher (male: 3.3-8.2; female: 3.8-8.8; see Table 1). Table 1: Reference ranges SAM and SAH