A Case-Control Study of the MTHFR C665T Gene Polymorphism on Macrocytic Anemia Among HIV-Infected Patients Receiving Zidovudine

Background: Macrocytic anemia is the most common anemia in HIV-infected patients receiving zidovudine, and is closely related to folate and vitamin B12 deficiencies. Homocysteine >10 mu mol/L and increased MMA (methylmalonic acid) levels >24.8 ng/mL indicate high/low folate and vitamin B12 deficiencies. Furthermore, MTHFR (Methylene-tetrahydrofolate-reductase) plays an essential role in the transmethylation of homocysteine to methionine and is related to DNA synthesis. The MTHFR C665T gene polymorphism decreases the activity of MTHFR, which culminates in homocysteinemia. Therefore, this case-control aims to assess the role of the MTHFR C665T gene polymorphism on the risk of macrocytic anemia among HIV-infected individuals receiving zidovudine. Methods: This study was conducted using an unmatched case-control design and the participants were HIV-infected adults aged 20 to 59 years old, receiving zidovudine for four weeks and above. A sample of 232 patients was divided into case group with macrocytic anemia and the control having no anemia. Multivariate logistic regression analysis was then implemented to determine the risk factors. Results: The results showed that there was a significant difference in the number of female and male patients namely 51.3% and 48.7%, respectively, with p< 0.001. Moreover, the mean age of the cases and control group was 41.9 +/- 9.4 and 36.2 +/- 8.3. Regarding education, there were significant differences between subjects with low and high education 47.8% vs 52.2% with p<0.001. The majority of patients or 90.95% had taken AZT for more than 6 months. The logistic regression analysis test results showed that sex, age, education level, duration of AZT use, and homocysteine levels were predictors of macrocytic anemia with p<0.05, while MTHFR C665T gene polymorphism and MMA levels were not risk factors. Conclusion: MTHFR C665T gene polymorphism does not contribute to the incidence of macrocytic anemia among HIV-infected individuals receiving zidovudine.