Polymorphisms involved in the folate metabolizing pathway and risk of multiple myeloma

Abstract

Folate and methionine metabolism plays an essential role in both DNA synthesis and methylation. Polymorphisms in the genes of the folate‐dependent enzymes have been shown to affect disease susceptibility. We conducted a Korean population‐based case‐control study to evaluate whether genetic variation in folate metabolism may have a role in the risk of multiple myeloma (MM). The study subjects were 173 patients with MM and 1,700 population‐based controls. The polymorphisms studied include methylenetetrahydrofolate reductase (MTHFR) 677 C > T and 1298 A > C, methionine synthase (MS) 2756 A > G, methionine synthase reductase (MTRR) 66A > G, thymidylate synthase (TS) 28‐bp repeat (2R→3R) and 6‐bp deletion/insertion. MS 2756 AG genotypes were associated with a 1.5‐fold lower risk of MM (OR = 0.66, 95%CI; 0.43–0.99, P = 0.047). There was no association between MTHFR C677T, A1298C, MTRR A66G, TS 2R→3R and 6‐bp deletion/insertion polymorphisms and MM. These results suggest that MTHFR C677T, A1298C, MTRR A66G, TS 2R→3R, and 6‐bp deletion/insertion do not significantly factor into the pathogenesis of MM in the Korean population, but that MS A2756G polymorphism may play an important role. Am. J. Hematol., 2007. © 2007 Wiley‐Liss, Inc.

The Allele Frequencies of Three Polymorphisms in Genes Involved in Homocysteine Metabolism in a Group of Unrelated Healthy Singaporeans

“…The MS 2756G allele in our Malay samples (17.9%) was similar to the frequencies in Japanese (17.3%) [33], Hispanics (18.8%), and Caucasians (19.9%) [34]. The MS 2756G allele frequency in our Chinese samples, 11.0%, was similar to the frequencies reported for Chinese (8.5%) [35], Thais (11.8%) [36] and Koreans (13.1%) [37]. Higher frequencies of the MS 2756G allele were detected in African Americans (23.8%) [34] and Northern Indians (24%) [38], which were similar to that in our Indian samples (26.4%).…”

“…The reduced enzyme activity led to a hypothesis that the T/T genotype might result in elevated Hcy level in humans, which was found to be true in subsequent studies, at least in some Asian populations [6,[8][9][10][11]. In this study, the MTHFR 677T allele was less common than the 677C allele in Singaporeans, which is also the case in Koreans [37], Asian Indians living in South Africa [39] or UK [40], Japanese [41], and Caucasians [40,42]. However, in some groups of Northern Chinese [42,43], the 677T allele was more common than the 677C allele.…”

Gender-specific association of <i>MSA2756G</i> with hypertension in patients attending a health facility in Ningxia Province, China

“…The most prevalent polymorphism is the A2756G SNP which results in the conversion of an aspartic acid residue to a glycine residue [10]. The MS 2756G allele in our Chinese Hui population (12.04 %) was similar to the frequencies in Singapore (11.0 %) [10], Thailand (11.8 %) [11] and Koreans (13.1 %) [12]. The MS 2756G allele frequency in our study was lower than in Japanese (17.3 %) [13], Hispanics (18.8 %), and Caucasians (19.9 %) [14], which was half of that in African Americans (23.8 %) [14] and Northern Indians (24 %) [15], Indians (26.4 %) [10].…”

Genetics and molecular epidemiology of multiple myeloma: The rationale for the IMMEnSE consortium (Review)

“…MTHFR, which has been found associated with cancer risk (108,109), is one of the most important enzymes involved in the regulation of folate homeostasis. Two MTHFR missense SNPs, C677T (rs1801133) and A1298C (rs1801131), were investigated in relation to MM susceptibility in various reports with evidence for association (110)(111)(112) as well as for no association (113)(114)(115)(116)(117). Recently, a meta-analysis confirmed a possible role for the MTHFR C677T (rs1801133) SNP in MM susceptibility, with an increased risk for carriers of the 677T allele (118).…”

“…Recently, a meta-analysis confirmed a possible role for the MTHFR C677T (rs1801133) SNP in MM susceptibility, with an increased risk for carriers of the 677T allele (118). The minor allele (G) of the missense substitution A2756G (rs1805057) in the enzyme methionine syntase (MS or MTR) has been found associated with higher risk of MM in a mixed Caucasian and AfricanAmerican population (112), but with decreased risk in an Asian population (114). However, this effect was not observed in a third study (117).…”