Abstract

Methionine synthase (MS) is a cobalamin dependent enzyme that catalyses the remethylation of homocysteine to methionine. The methionine synthase reductase (MSR) maintains adequate levels of methylcob(III)alamin, the activated cofactor for MS. The aim of this study was to investigate the effect of MS A2756G and MSR A66G polymorphisms on total homocysteine (tHcy), S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH) levels in 390 pregnant women and their 292 newborns, from Sorocaba city, Brazil. Genotypes of two polymorphisms were determined by PCR-RFLP. Pregnant women with MS 2756AA genotype have higher tHcy and lower Cbl levels than those with 2756G alleles. The MMA values were increased in neonates with MS 2756AA genotypes (Table 1). There are no difference between the maternal values of Cbl, serum folate, tHcy, MMA and SAM according to MSR A66G genotypes.The values of SAM were lower in neonates with MSR 66G alleles than those with AA genotypes (Table 2). We conclude that MS 2756AA genotypes are associated with higher tHcy levels in pregnant women and higher MMA levels in neonates. The MSR 66GG genotypes is associated with lower SAM levels in neonates.

Table 1- Distribution of geometric means and confidence intervals 95% (CI 95%) and numbers of subjects for maternal and neonatal values of cobalamin (Cbl), serum folate, total homocysteine (tHcy), methymalonic acid (MMA) and S- adenosylmethionine (SAM) according to genotypes for the polymorphism MS A2756G.

VariablesGenotypes for MS A2756GStudent t Test
AAAG + GG
Pregnant Women    
Cbl (pmol/L) 139 (133 – 144) 235 156 (146 – 166) 129 P= 0.001 
SF (nmol/L) 14.3 (13.6 – 15.0) 234 14.5 (13.6 – 15.5) 129 P= 0.667 
tHcy( μmol/L) 6.8 (6.5 – 7.1) 235 6.2 (5.9 – 6.6) 128 P= 0.036 
MMA(nmol/L) 234 (219 – 245) 194 241 (219 – 265) 106 P= 0.610 
SAM(nmol/L) 81.8 (77.9 – 86,0) 229 83.1 (79.1 – 87.4) 124 P= 0.663 
Neonates    
Cbl (pmol/L) 227 (212 – 244) 188 234 (213 – 257) 101 P= 0.646 
SF (nmol/L) 32.0 (31.0 – 33.0) 186 32.0 (30.8 – 33.2) 99 P= 0.967 
tHcy μmol/L) 5.8 (5.5 – 6.1) 185 5.5 (5.1 – 5.9) 100 P= 0.229 
MMA(nmol/L) 383 (364 – 402) 183 342 (317 – 369) 100 P= 0.011 
SAM(nmol/L) 188 (181 – 196) 178 182 (168 – 197) 98 P= 0.491 
VariablesGenotypes for MS A2756GStudent t Test
AAAG + GG
Pregnant Women    
Cbl (pmol/L) 139 (133 – 144) 235 156 (146 – 166) 129 P= 0.001 
SF (nmol/L) 14.3 (13.6 – 15.0) 234 14.5 (13.6 – 15.5) 129 P= 0.667 
tHcy( μmol/L) 6.8 (6.5 – 7.1) 235 6.2 (5.9 – 6.6) 128 P= 0.036 
MMA(nmol/L) 234 (219 – 245) 194 241 (219 – 265) 106 P= 0.610 
SAM(nmol/L) 81.8 (77.9 – 86,0) 229 83.1 (79.1 – 87.4) 124 P= 0.663 
Neonates    
Cbl (pmol/L) 227 (212 – 244) 188 234 (213 – 257) 101 P= 0.646 
SF (nmol/L) 32.0 (31.0 – 33.0) 186 32.0 (30.8 – 33.2) 99 P= 0.967 
tHcy μmol/L) 5.8 (5.5 – 6.1) 185 5.5 (5.1 – 5.9) 100 P= 0.229 
MMA(nmol/L) 383 (364 – 402) 183 342 (317 – 369) 100 P= 0.011 
SAM(nmol/L) 188 (181 – 196) 178 182 (168 – 197) 98 P= 0.491 

Table 2 - Distribution of geometric means and confidence intervals 95% (CI (%%) and number of subjects for neonatal values of cobalamin (Cbl), serum folate, total homocysteine (tHcy), methylmalonic acid (MMA) and S- adenosylmethionine (SAM) according to genotypes for the polymorphism MSR A66G.

VariablesGenotypes MSR A66GStudent t Test
AAAGGG
Groups not sharing a common superscript letter are significantly different at P<0.05 based on Tukey’s test 
Neonates     
Cbl (pmol/L) 225 (202 – 249) 86 229 (214 – 246) 166 247 (205 – 298) 35 P= 0.602 
SF (nmol/L) 33.0 (31.6 – 34.4) 84 31.7 (30.7 – 32.7) 166 31.8 (29.7 – 34.2) 33 P= 0.352 
tHcy μmol/L) ( 5.7 (5.3 – 6.2) 84 5.6 (5.3 – 5.9) 165 5.9 (5.3 – 6.6) 34 P= 0.618 
MMA (nmol/L) 360 (334 – 389) 84 378 (357 – 400) 163 339 (299 – 384) 34 P= 0.230 
SAM (nmol/L) 200 (186 – 215)a 82 184 (176 – 192)a 159 170 (149 – 195)b 33 P= 0.032 
VariablesGenotypes MSR A66GStudent t Test
AAAGGG
Groups not sharing a common superscript letter are significantly different at P<0.05 based on Tukey’s test 
Neonates     
Cbl (pmol/L) 225 (202 – 249) 86 229 (214 – 246) 166 247 (205 – 298) 35 P= 0.602 
SF (nmol/L) 33.0 (31.6 – 34.4) 84 31.7 (30.7 – 32.7) 166 31.8 (29.7 – 34.2) 33 P= 0.352 
tHcy μmol/L) ( 5.7 (5.3 – 6.2) 84 5.6 (5.3 – 5.9) 165 5.9 (5.3 – 6.6) 34 P= 0.618 
MMA (nmol/L) 360 (334 – 389) 84 378 (357 – 400) 163 339 (299 – 384) 34 P= 0.230 
SAM (nmol/L) 200 (186 – 215)a 82 184 (176 – 192)a 159 170 (149 – 195)b 33 P= 0.032 

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