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Human genetic selection on the MTHFR 677C>T polymorphism.
Alvaro Mayor-Olea1, Gonzalo Callejón, Arturo R Palomares
1Department of Biochemistry and Molecular Biology, University of Malaga, Malaga 29071, Spain. dralvaromayor@gmail.com
BMC Medical Genetics
|December 2, 2008
Summary
Selection favors the T allele of the MTHFR gene, particularly in later 20th-century births. This suggests increased viability of fetuses with the T allele during early embryonic development.
Area of Science:
- Genetics
- Human Population Studies
- Reproductive Biology
Background:
- The 677C>T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene exhibits varying prevalence across human populations.
- Previous research indicated shifts in genotypic frequencies related to age, possibly due to increased periconceptional folate and multivitamin intake.
- This study aimed to investigate changes in allelic frequencies of the MTHFR 677C>T polymorphism in a Spanish population, including samples from spontaneous abortions (SA).
Purpose of the Study:
- To analyze changes in the allelic frequencies of the MTHFR 677C>T polymorphism in a Spanish population.
- To include samples from spontaneous abortions (SA) to assess potential selection pressures.
- To evaluate the impact of factors like folate intake on MTHFR genotype frequencies over time.
Main Methods:
- Genotyping of 1305 individuals born in the 20th century for the MTHFR 677C>T polymorphism.
- Utilized allele-specific real-time PCR with Taqman probes for genotyping.
- Compared a cohort born between 1980-1989 (n=276) with fetal samples from spontaneous abortions (SA) of unknown etiology from the same period (n=344).
Main Results:
- Observed a significant increase in the T allele frequency (0.38 to 0.47) and TT genotype frequency (0.14 to 0.24) in individuals born in the last quarter of the 20th century.
- In the 1980-1989 period, the wild-type CC genotype was tenfold less frequent in SA samples compared to controls (0.03 vs 0.33).
- The TT genotype frequency increased in both controls (0.19 to 0.27) and SA samples (0.20 to 0.33) during this period, indicating a strong correlation (r=0.98).
Conclusions:
- Detected significant selection favoring the T allele of the MTHFR 677C>T polymorphism.
- This selection is likely attributed to increased fetal viability in early embryonic development stages.
- The observed increase in mutant alleles in both living and SA populations supports the hypothesis of selection for the T allele.
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