Other factors that might be associated with increased homocysteine include: preexisting atherosclerotic disease, consumption of coffee and alcohol, smoking, DM, use of antiepileptic drugs or methotrexate, renal failure, rheumatoid arthritis (RA), hypothyroidism, and cystathionine beta-synthase and methylenetetrahydrofolate reductase mutations. Here, CBS is linked to rheumatoid arthritis.