Association of c.+677 C>T (rs1801133) and c.+1298 A>C (rs1801131) MTHFR genetic variants with cardiometabolic and disease risk in systemic lupus erythematosus patients: A cross-sectional study.

Publisher: SAGE Publications Country of Publication: England NLM ID: 9204265 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1477-0962 (Electronic) Linking ISSN: 09612033 NLM ISO Abbreviation: Lupus Subsets: MEDLINE

Publication: London : SAGE Publications
Original Publication: Houndmills, Basingstoke, Hampshire, UK : Scientific & Medical Division, Macmillan Press Ltd., c1991-

Lupus Erythematosus, Systemic*/genetics ; Lupus Erythematosus, Systemic*/complications ; Methylenetetrahydrofolate Reductase (NADPH2)*/genetics ; Polymorphism, Single Nucleotide* ; Genetic Predisposition to Disease* ; Folic Acid*/blood; Humans ; Female ; Cross-Sectional Studies ; Case-Control Studies ; Adult ; Mexico/epidemiology ; Middle Aged ; Homocysteine/blood ; Cardiovascular Diseases/genetics ; Cardiovascular Diseases/etiology ; Cardiovascular Diseases/epidemiology ; Cardiometabolic Risk Factors ; Genotype ; Risk Factors ; Young Adult

Systemic lupus erythematosus (SLE) patients present a high prevalence of cardiometabolic risk, associated with worse clinical manifestations and mortality. Folate, an essential micronutrient that participates in vital immune cellular functions, could positively affect the cardiometabolic and disease risk in SLE, through the methylenetetrahydrofolate reductase (MTHFR) enzyme, which participates in the folate metabolism, where single nucleotide variants (SNVs) have been described as a potential genetic risk factor for SLE. The aim of this study was to determine the association of the c.+677 C>T (rs1801133) and c.+1298 A>C (rs1801131) MTHFR genetic variants with cardiometabolic risk and clinical disease variables in SLE patients. A case-control study was conducted on 394 unrelated Mexican-mestizo women: 199 with SLE according to the 1997 SLE-ACR criteria and 196 control subjects (CS). Folic acid and homocysteine levels were evaluated by immunoassays. Genotyping of MTHFR genetic variants was carried out by allelic discrimination. No significant differences were found for folic acid ( p = .15) and homocysteine serum levels ( p = .59) between groups. According to the CC c.+677 MTHFR genotype, this was associated with low cardiovascular disease (CVD) risk by the Castelli index (OR = 0.42; p = .03) in SLE patients. The TC (OR = 1.3; p = .03) and the TA (OR = 1.6; p < .01) haplotypes from c.+677 C>T plus c.+1298 MTHFR were associated with SLE risk, while the CC MTHFR haplotype (OR = 0.5; p = .01) was found as a non-risk factor for the disease. In conclusion, the TC and the TA MTHFR haplotypes are associated with disease risk; meanwhile, the CC c.+677 MTHFR genotype confers lower cardiometabolic risk in Mexican-mestizo SLE patients.
Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Keywords: MTHFR variants; folic acid; genetic risk; homocysteine

EC 1.5.1.20 (Methylenetetrahydrofolate Reductase (NADPH2))
EC 1.5.1.20 (MTHFR protein, human)
935E97BOY8 (Folic Acid)
0LVT1QZ0BA (Homocysteine)

Date Created: 20240523 Date Completed: 20240802 Latest Revision: 20240802

20240802

10.1177/09612033241257158

38782407