Distribution of MTHFR C677T Gene Polymorphism in Healthy North Indian Population and an Updated Meta-analysis

Abstract

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme of folate pathway. Several polymorphisms were reported in gene but C677T polymorphism is most studied and it has been reported to be risk factor for several diseases/disorders. The present study was designed to explore the frequency of C677T polymorphism in North Indian healthy population. In addition to this a meta-analysis of published articles was also performed to estimate the global prevalence of C677T polymorphism. A total of 1000 unrelated healthy subjects were selected for C677T polymorphism analysis. Different databases were searched for eligible articles. Prevalence proportion with 95 % CI was used to determine global prevalence of T allele and TT genotype. Meta-analysis was performed by Open meta-analyst. In 1000 blood samples analyzed, the frequency of T allele and TT genotype was 11 and 1 % respectively. Results of the meta-analysis showed that the global prevalence of T allele and TT genotype were 24.0 % (95 % CI 21.7-26.5) and 7.7 % (95 % CI 6.5-8.9) respectively. In sub-group meta-analysis, the lowest frequency of T allele was found in Africans (10.3 %; 95 % CI 3.8-16.8), and highest in Europeans (34.1 %; 95 % CI 31.9-36.3). The frequency of T allele in the North India is 11 %. The results of the meta-analysis showed that the frequency of the T allele and the TT genotype of C677T is highest in the Caucasian population.

Strong Association of C677T Polymorphism of Methylenetetrahydrofolate Reductase Gene With Nosyndromic Cleft Lip/Palate (nsCL/P)

“…MTHFR C677T polymorphism is reported as risk factor for several diseases and disorders like-neural tube defects [37], Down syndrome [36,38], congenital heart defects [39], and cardiovascular diseases etc. Globally, the prevalence of 677T allele ranged from 24.1 to 64.3% among Europeans, 2-48% among North Americans, 7% among South Americans, 0-35.5% among Africans and 2-63.1% in Asians [40][41][42][43][44].…”

Life-threatening course in coronavirus disease 2019 (COVID-19): Is there a link to methylenetetrahydrofolic acid reductase (MTHFR) polymorphism and hyperhomocysteinemia?

“…The 5,10-methylenetetrahydrofolic acid reductase (MTHFR) enzyme is most important in the one-carbon-methionine pathway regulating fundamental processes in cell physiology such as DNA repair, neurotransmitter functions and membrane transport [4] . The T allele of the MTHFR-gene (C677T polymorphism), in which cytosine is replaced by thymine at the 677th position, has been suggested to be protective against malignancies such as colon cancer and acute lymphatic leukemia [4] , [5] . This mutation leads to a thermolabile enzyme variant in which the dissociation rate of the cofactor flavin adenine dinucleotide (FAD) is increased reducing its activity to an extent of 50% or more [4] , [5] .…”

“…The T allele of the MTHFR-gene (C677T polymorphism), in which cytosine is replaced by thymine at the 677th position, has been suggested to be protective against malignancies such as colon cancer and acute lymphatic leukemia [4] , [5] . This mutation leads to a thermolabile enzyme variant in which the dissociation rate of the cofactor flavin adenine dinucleotide (FAD) is increased reducing its activity to an extent of 50% or more [4] , [5] . In people possessing a medium skin tone, which evolutionarily developed in Eurasia under moderate UV radiation, the basic MTHFR function is largely preserved as long as there is sufficient dietary folic acid [4] , [5] .…”

“…This mutation leads to a thermolabile enzyme variant in which the dissociation rate of the cofactor flavin adenine dinucleotide (FAD) is increased reducing its activity to an extent of 50% or more [4] , [5] . In people possessing a medium skin tone, which evolutionarily developed in Eurasia under moderate UV radiation, the basic MTHFR function is largely preserved as long as there is sufficient dietary folic acid [4] , [5] . However, with insufficient folate intake the reduced activity of the MTHFR enzyme leads to reduced levels of 5-methyltetrahydrofolate (5-MTHF) and thus reduced activity of methionine synthetase culminating in accumulation of the key metabolite homocysteine (Hc) to toxic levels [4] .…”

Hyperhomocysteinemia is Associated with Inflammation, Bone Resorption, Vitamin B12 and Folate Deficiency and MTHFR C677T Polymorphism in Postmenopausal Women with Decreased Bone Mineral Density

“…The C677T polymorphism shows a wide regional and ethnic variation. It has been found to have high frequencies in Europeans and American Caucasian population, and the prevalence rises in Mediterranean and Hispanic people, whereas it is less prevalent in Africa and intermediate among Asian populations [33]. The reason for this varied distribution seems to be directed not only by environmental effects (in particular folate and B12 rich/deficient diets), but it is also due to diversity in the various ethnic groups residing in the world.…”