Relationship between methionine synthase, methionine synthase reductase genetic polymorphisms and deep vein thrombosis among South Indians.
BACKGROUND
The rationale behind this study was to examine the relationship between polymorphisms in genes that regulate remethylation of homocysteine to methionine, i.e., methionine synthase (MTR A2756G) and methionine synthase reductase (MTRR A66G), and risk of deep vein thrombosis (DVT) in a South Indian cohort (163 DVT cases and 163 controls), as elevated homocysteine has been documented as an independent risk factor for DVT in the same cohort.


METHODS
Plasma homocysteine analysis was carried out by reverse phase HPLC. The MTR A2756G and MTRR A66G genetic polymorphisms were detected using PCR-restriction fragment length polymorphism method. For statistical analyses, Fisher's exact test was used for categorical variables and Student's t-test and analysis of variance were used for continuous variables.


RESULTS
The MTRR 66GG genotype was associated with a 2.74-fold [95% confidence interval (CI): 1.73, 4.34] risk of DVT. The MTR A2756G polymorphism was not a risk factor. MTRR GG/MTR AG and MTRR GG/MTR GG genotypes cumulatively were found to increase the risk of DVT by 2.38-fold (95% CI: 1.43, 3.96). A positive association was observed between plasma homocysteine and the MTRR G allele, and the MTR G allele was shown to have an additive effect. The risk associated with the MTRR 66GG genotype was further increased in subjects compound heterozygous for methylene tetrahydrofolate reductase (MTHFR) [odds ratio (OR): 3.46, 95% CI: 1.38, 8.63].


CONCLUSIONS
The MTRR 66GG genotype is a risk factor for DVT among South Indians. This risk is increased further in the presence of the MTHFR 677CT/1298AC genotype.
Naushad
Shaik Mohammad
SM
Diagnostic Division, Center for DNA Fingerprinting and Diagnostics, Hyderabad, Andhra Pradesh, India.
Jain Jamal
Mohamed Nurul
MN
Prasad
Chintakindi Krishna
CK
Rama Devi
Akella Radha
AR
D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000097:blood / Q000235:genetics*; D000328:Adult; D000368:Aged; D000483:Alleles; D001483:Base Sequence; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005287:Ferredoxin-NADP Reductase / Q000097:blood / Q000235:genetics*; D005838:Genotype; D006579:Heterozygote; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D007194:India / Q000453:epidemiology / Q000208:ethnology; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D012307:Risk Factors; D020246:Venous Thrombosis / Q000201:enzymology / Q000235:genetics*
D006710:Homocysteine; C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase