Interplay between 3′-UTR polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene and the risk of ischemic stroke

• Published in: Scientific reports Vol. 7; no. 1; pp. 12464 - 10
• Main Authors: Kim, Jung Oh, Park, Han Sung, Ryu, Chang Soo, Shin, Jung-Won, Kim, Jinkwon, Oh, Seung Hun, Kim, Ok Joon, Kim, Nam Keun
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 29.09.2017; Nature Publishing Group
• Subjects: 3' Untranslated Regions; 45/23; 45/77; 631/208/727/2000; 631/208/728; 692/53/2423; Aged; Brain Ischemia - blood; Brain Ischemia - diagnosis; Brain Ischemia - genetics; Brain Ischemia - physiopathology; Case-Control Studies; Dihydrofolate reductase; Female; Folic acid; Folic Acid - blood; Gene Expression; Gene-Environment Interaction; Genotype; Health risks; Homocysteine; Homocysteine - blood; Humanities and Social Sciences; Humans; Hyperhomocysteinemia; Hyperhomocysteinemia - blood; Hyperhomocysteinemia - diagnosis; Hyperhomocysteinemia - genetics; Hyperhomocysteinemia - physiopathology; Ischemia; Male; Methylenetetrahydrofolate reductase; Methylenetetrahydrofolate Reductase (NADPH2) - blood; Methylenetetrahydrofolate Reductase (NADPH2) - genetics; Middle Aged; multidisciplinary; Polymorphism; Polymorphism, Single Nucleotide; Prognosis; Risk Factors; Science; Science (multidisciplinary); Single-nucleotide polymorphism; Stroke; Stroke - blood; Stroke - diagnosis; Stroke - genetics; Stroke - physiopathology; Vitamin B
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-12668-x

Stroke incidence is a multifactorial disease and especially hyperhomocysteinemia is associated with a higher risk of stroke. Previous studies have reported a folate metabolism disorder associated with the MTHFR gene. We investigated four single nucleotide polymorphisms in the MTHFR 3′-UTR [2572 C > A (rs4846049), 4869 C > G (rs1537514), 5488 C > T (rs3737967), and 6685 T > C (rs4846048)] to elucidate associations between ischemic stroke prevalence and prognosis. We examined 511 consecutive patients with ischemic stroke. Additionally, we selected 411 sex-/age-matched control subjects from patients presenting at our hospitals during the same period. The MTHFR 2572 C > A and 6685 T > C were significantly associated with ischemic stroke prevalence in the cardioembolism subgroup ( MTHFR 2572CC vs. CA + AA: AOR, 2.145; 95% CI, 1.203–3.827; P  = 0.010; MTHFR 6685TT vs. CC: AOR, 10.146; 95% CI, 1.297–79.336; P  = 0.027). The gene-environment combined effect was significant, with MTHFR 2572CA + AA and folate levels ≤3.45 ng/mL correlating with ischemic stroke incidence. In addition, the total homocysteine (tHcy) levels in subjects with MTHFR 2572AA were elevated compared to tHcy levels in subjects with MTHFR 2572CC. Therefore, we suggest that MTHFR 2572 C > A and 6685 T > C are associated with ischemic stroke pathogenesis. The combined effects of the MTHFR 3′-UTR polymorphisms and tHcy/folate levels may contribute to stroke prevalence.