MTHFR C677T, MTHFR A1298C, and OPG A163G Polymorphisms in Mexican Patients with Rheumatoid Arthritis and Osteoporosis

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.

Significant Associations Between the A163G and G1181C Polymorphisms of the Osteoprotegerin Gene and Risk of Osteoporosis, Especially in Postmenopausal Women: A Meta-Analysis

“…In accordance with the inclusion criteria for this metaanalysis, 10 case-control studies (Langdahl et al, 2002;Zhao et al, 2005;Hsu et al, 2006;Wu and Liu, 2006;Kim et al, 2007;Shui et al, 2008;Mencej-Bedrac et al, 2009;Seremak-Mrozikiewicz et al, 2009;Brambila-Tapia et al, 2012;Hussien et al, 2013) were included and 139 were excluded. A flow chart of the study selection process and specific reasons for any exclusion from this meta-analysis is shown in Figure 1.…”

“…Publication years of the included studies range from 2002 to 2013. Of the 10 studies that met the criteria for inclusion in the meta-analysis, 7 examined the A163G polymorphism (Langdahl et al, 2002;Hsu et al, 2006;Wu and Liu, 2006;Shui et al, 2008;Seremak-Mrozikiewicz et al, 2009;Brambila-Tapia et al, 2012;Hussien et al, 2013) and 5 investigated the G1181C polymorphism (Langdahl et al, 2002;Zhao et al, 2005;Kim et al, 2007;Mencej-Bedrac et al, 2009;Seremak-Mrozikiewicz et al, 2009). In the seven studies on the A163G polymorphism, five studies reported that the genotype distribution in controls did not deviate significantly from HWE, and four out of the five studies on G1181C polymorphism complied with HWE.…”

“…A163G is located in the promoter region of the OPG gene, and G1181C is located in the first exon and causes a change in amino acid from lysine to asparagine (Huang et al, 2011). Several association studies have consistently shown a significant association of A163G and G1181C polymorphisms with the osteoporosis risk (Langdahl et al, 2002;Zhao et al, 2005;Hsu et al, 2006;Kim et al, 2007;Seremak-Mrozikiewicz et al, 2009;Hussien et al, 2013), while other studies failed to find a similar result (Wu and Liu, 2006;Shui et al, 2008;Mencej-Bedrac et al, 2009;Brambila-Tapia et al, 2012). Thus, we conducted this meta-analysis to clarify and quantify the strength of association between the OPG A163G and G1181C polymorphisms and osteoporosis.…”

Effect of MTHFR, TGFβ1, and TNFB polymorphisms on osteoporosis in rheumatoid arthritis patients

“…1p36 chromosome region is associated with RA and OP (Karsak et al, 2005;Owen et al, 2013). The association between C677T and RA patients with OP was confirmed in Mexican population (Brambila-Tapia et al, 2012). The C677T and the A1298C are two common polymorphisms in the MTHFR gene (Lee and Song, 2010).…”

Association between the methylenetetrahydrofolate reductase c.677C>T polymorphism and bone mineral density: an updated meta-analysis

“…The c.677C>T variant enhances enzyme thermolability and is associated with decreased activity of the MTHFR enzyme (Kang et al 1988;Bagley and Selhub 1998), the activity being 65 % in heterozygotes (CT) and 30 % in homozygotes (TT), relative to the CC genotype (Frosst et al 1995). To date, a number of molecular epidemiological studies have been performed to evaluate the association between the MTHFR c.677C>T polymorphism and BMD in diverse populations (Tongboonchoo et al 2013;Shin et al 2013;Pandey et al 2013;Brambila-Tapia et al 2012;Abrahamsen et al 2003;Li et al 2004;Villadsen et al 2005;Hong et al 2007;Yazdanpanah et al 2008;Zhu et al 2009;Agueda et al 2010;Oishi et al 2012;Macdonald et al 2004;McLean et al 2004;Miyao et al 2000;Golbahar et al 2004;Abrahamsen et al 2006;Nissen et al 2009). However, the results are inconsistent or even contradictory.…”