ABSTRACT
MTHFR polymorphisms C677T and A1298C are associated with reduced MTHFR enzyme activity and hyperhomocysteinemia, which has been associated with osteoporosis. The A163G polymorphism in osteoprotegerin (OPG) has been studied in osteoporosis with controversial results. The objective of the present study was to investigate the association(s) among MTHFR C677T, MTHFR A1298C, and OPG A163G polymorphisms in Mexican patients with rheumatoid arthritis and osteoporosis. The femoral neck and lumbar spine bone mineral densities (BMDs) were measured in 71 RA patients, and genotyping for the three polymorphisms was performed via restriction fragment length polymorphism analysis. Patients with osteoporosis/osteopenia exhibited statistically significant differences in the genotype frequencies of MTHFR C677T as well as an association with femoral neck BMD; TT homozygotes had lower BMDs than patients with the CT genotype, and both of these groups had lower BMDs than patients with the CC genotype. The associations of the MTHFR C677T polymorphism with osteoporosis/osteopenia and femoral neck BMD suggest that these polymorphisms confer a risk of developing osteoporosis in patients with rheumatoid arthritis, a risk that may be reduced with folate and B complex supplementation.
Subject(s)
Arthritis, Rheumatoid/genetics , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Osteoporosis/genetics , Osteoprotegerin/genetics , Polymorphism, Single Nucleotide , Adult , Aged , Arthritis, Rheumatoid/enzymology , Bone Density , Female , Femur Neck/pathology , Genetic Association Studies , Haplotypes , Humans , Mexico , Middle Aged , Osteoporosis/enzymology , Polymorphism, Restriction Fragment Length , Statistics, NonparametricABSTRACT
BACKGROUND: Non-syndromic cleft lip with or without cleft palate (NSCLP) is a common malformation. The aetiology is multifactorial. An incidence of 1.1-1.39 per 1000 new births had been reported in Mexico. The folic acid intake in preconceptional stage has been reported to prevent malformations such as neural tube defects (NTD) and NSCLP. The C677T variant of the methylene-tetrahydrofolate reductase (MTHFR) gene is responsible of a thermolabile form, related to decrease of folate and increase homocysteine. This variant has been associated with CLP, in different populations, but results are still controversial. Our objective was to determine the allelic (AF) and genotypic frequency (GF) of the MTHFR-C677T variant in Mexican children with NSCLP. METHODS: Transverse comparative study in 67 Mexican children with NSCLP and a control group with 70 unrelated Mexican individuals without NSCLP. RESULTS: The AF in NSCLP was 39 %. There was no statistical difference between AF in the two groups (39 versus 41). CONCLUSIONS: In this population, genotype C677T was not a major risk factor for this malformation, however, sample size, other genes implicated and genes-environment interactions must be considered.
