Analysis of two mutations in the MTHFR gene associated with mild hyperhomocysteinaemia--heterogeneous distribution in the South African population.
OBJECTIVE
The frequencies of mutations 677C-->T and 1298A-->C in the methylenetetrahydrofolate reductase (MTHFR) gene, previously shown to be associated with decreased enzyme activity that may lead to hyperhomocysteinaemia and consequently increased risk of cardiovascular disease (CVD), were determined in the South African population.


METHODS
HinfI (677C-->T) and MboII (1298A-->C) restriction enzyme analyses were performed on amplified DNA samples of 76 white, 73 coloured and 60 black subjects.


RESULTS
The mutant alleles of mutations 677C-->T and 1298A-->C were more common in the white (allele frequencies 0.36 and 0.37, respectively) than in the black population (0.04 and 0.09), while intermediate frequencies were detected in the coloured population (0.18 and 0.30). Homozygosity for mutation 677C-->T was not detected in the black cohort, while this genotype was detected in 1 coloured (1.4%) and 8 white (10.5%) subjects. In the black population, 5% of the 60 subjects analysed were homozygous for mutation 1298A-->C, compared with approximately 12% in both the white and coloured populations.


CONCLUSIONS
Since hyperhomocysteinaemia is a risk factor for premature CVD, the heterogeneous distribution of the 677C-->T and 1298A-->C mutations across ethnic groups may partly explain ethnic differences in heart disease risk through decreased enzyme activity and hence increased homocysteine levels.
Scholtz
Charlotte L
CL
Medical Research Council Heart Group, Division of Human Genetics, University of Stellenbosch, Tygerberg, W Cape.
Odendaal
Hein J
HJ
Thiart
Rochelle
R
Loubser
Lynzie
L
Hillermann
Renate
R
Delport
Rhena
R
Vermaak
W J Hayward
WJ
Kotze
Maritha J
MJ
D002318:Cardiovascular Diseases / Q000209:etiology / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics; D005828:Genetics, Population; D006710:Homocysteine / Q000009:adverse effects / Q000097:blood* / Q000235:genetics*; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D009154:Mutation; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*; D013019:South Africa
D006710:Homocysteine; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)