People with MTHFR mutation have elevated homocysteine levels.
The mutations can lead to high levels of homocysteine in the blood, which may contribute to several health conditions, including:
Mutations in the MTHFR gene can affect the body’s ability to process amino acids — namely, homocysteine — which can lead to some adverse health outcomes.
Conditions that researchers have associated with MTHFR gene mutations include:
- homocysteinemia, which is the term for abnormally high levels of homocysteine in the blood or urine
- ataxia, which is a neurological condition that affects coordination
- peripheral neuropathy, which is a neurological condition that damages the nerves
- microcephaly, which is a condition present at birth in which the head is smaller than usual
- scoliosis, which refers to an abnormal curvature of the spine
- anemia, which means that there is a lack of healthy red blood cells in the body
- cardiovascular diseases, such as blood clots, stroke, and heart attack
- mental health conditions, such as depression, schizophrenia, Alzheimer
- behavior disorders, such as attention deficit hyperactivity disorder
- recurrent pregnancy loss
- myocardial infraction
677C>T mutation (rs1801133) and A1298C>T mutation are the major MTHFR gene mutations that cause these issue. The below map shows the distribution of these mutations world wide. As you can see the mutations values are very high (50+%) among certain Mexican, Tuscans, Bosnian, Czechs, Ukrainian, Norwegian, Swedish, certain Chinese and Japanese population world wide.
certain American Indian groups had very high percent of these mutations making them high susceptible to the different health conditions.
Remarkably, the frequency of the 677T in Mexican individuals and particularly in MA people, was the highest worldwide. In contrast, the frequency of the 1298C risk allele in Mexicans was the lowest in the world. In addition, the frequency of 677T allele showed an increasing gradient from northern to southern Mexico in both populations; while the 1298C allele frequency showed the opposite gradient (Fig 3). This finding demonstrates the great ethnic diversity and heterogeneity of the genetic background in the country. Consistent with previous studies [7, 8, 13, 16], our findings suggest that one of the major contributions of the 677T allele in MEZ was the Indian admixture; while, the 1298C allele is mainly derived from European genomes. Some ethnic groups had the highest frequencies in the country for the 677T allele. Mocho, Kaqchiquel, and Chuj, belonging to the Mayan linguistic family inhabiting the SE region, had frequencies >80%, and Mazateco, Mixteco, Zapoteco, Totonaco, and Mazahua from the S and CE regions had frequencies >70% (Fig 1). Notably, some ethnic groups showed particularities; for example, the Seris (N), Pame (CE), and Huave (S) had lower 677T allele frequencies than other groups that co-inhabited the same regions (13% vs. 32–47%; 35% vs. 57–74%; and 33% vs. 59–81%, respectively) (Fig 1). Also, we found seven ethnic groups that were monomorphic for the A allele of the A1298C polymorphism (Seri, Pame, Chuj, Kanjobal, Mocho, Mazahua, and Zapoteco) (Fig 2). In contrast to the 677T allele, the MA groups from the N (32–47%), with the exception of the Seris, had the highest 1298C allele frequencies (11–22%). These findings may reflect the particular features and history of migration and isolation throughout the centuries of each ethnic group, including the 5 Nahuatl groups, where heterogeneity was also observed among them.
Among Jewish, the frequency of the C677T MTHFR mutation in healthy Israeli ethnic groups. The frequency of the mutation was determined in 897 young healthy Jewish and Muslim Arab Israelis of eight different ethnic groups. Marked ethnic differences in the frequency of mutant homozygotes were found, ranging from 2% in Yemenite Jews, 4% in Sephardic Jews, 9% in Oriental Jews, 10% in Muslim Arabs, 16% in North African Jews, and 19% in Ashkenazi Jews. The frequency of mutant homozygotes was significantly higher in Ashkenazi Jews compared to Yemenites Oriental Jews, Sephardic Jews, and Muslim Arabs (χ2 = 12.35 p < 0.001, χ2 = 8.17 p = 0.004, χ2 = 6.04 p = 0.01, χ2 = 6.54 p = 0.01, respectively)
Among Arabs, significant differences in groups such as Lebanon Vs Bahrain are noticed. The C677T mutation was present in 169/408 Lebanese and 30/152 Bahraini participants, giving an overall carrier frequency of 41.4% for Lebanese and 19.7% for Bahraini participants [P < 0.001; odds ratio (OR) = 2.83; 95% confidence interval (CI) 1.81, 4.42]. Of the carriers, 159/408 (38.97%) Lebanese and 26/152 (17.11%) Bahraini carriers were heterozygotes (OR = 3.03; 95% CI 1.92, 5.00), while 10/408 (2.45%) Lebanese and 4/152 (2.63%) Bahraini carriers were in the homozygous state (OR = 1.25; 95% CI 0.39, 4.00) . No difference in the MTHFR C677T mutation frequency was seen with respect to gender.
In Iran, The prevalence of MTHFR (C677T) mutation was 17.9% of which 7.1% had the TT mutant allele in homozygous and 10.8% had CT allele in heterozygous state.
In Turkey, a study showed a genotypic distribution CC: CT: TT = 40.0%: 47.3%: 12.7% in 243 coronary patients. In a Chinese study, the genotypic distribution in 106 patients was CC: CT: TT = 63.8%: 25.7%: 10.5%. In a Tunisian study the genotypic distribution in patients was respectively CC: CT: TT = 42.2%: 38.9%: 18.9%. A Tunisian study of 185 apparently healthy subjects in 2005 showed an allele frequency of 17.8% and a genotypic frequency of 5.4%
Among South Asians, T-allele frequency for C677T mutation of MTHFR gene
in the South Indian population (0.10) established by this
study is lower compared to UK (0.186) and USA (0.322)
and much higher when compared to Sri Lanka (0.049)12
.
Similar findings were observed among case-control studies conducted in Mumbai and Pune. This shows certain urban groups in India harbor very high C677T mutations making them susceptible to different health conditions. There is no big study to find out more on these. Given high ANE based risk for this gene no wonder the newer groups who came post MLBA might have these higher risks from the mutations.
One of the Indian studies showed that Women have higher C677T mutations in India than Male. Overall Indian percentage is less compared to other major groups in China, Japan, Mexico, Peru, Italy, Bosnia, Scandinavia, Ukraine etc... However Indian probably harbor more localized such mutations in certain urban places like Pune, Mumbai, Chennai, Delhi etc... which requires more investigation and remedies
That probably shows that the Indian mtDNA has more ANE and UP based origin. However the deep Indian HGs like H and F are probable low on this gene and so low on such risk
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