The impact of vitamin D receptor genotype on the management of anemia in hemodialysis patients.
BACKGROUND
Both in vitro and in vivo studies have shown that calcitriol, the active form of vitamin D, is involved in hematopoiesis. We hypothesized that the vitamin D receptor (VDR) genotype, which may differentiate response to endogenous or exogenous active vitamin D, has a role in the management of anemia in hemodialysis (HD) patients.


METHODS
The VDR BsmI gene polymorphism was determined in 91 HD patients and 85 healthy controls. In addition to well-known factors responsible for both anemia and inadequate response to erythropoietin (EPO), we examined the contribution of the VDR genotype to hematocrit (Hct), hemoglobin (Hb) level, total weekly dose of EPO, and EPO-Hb ratio as an index of patient EPO need.


RESULTS
Genotype distributions for the VDR gene were under the Hardy-Weinberg equilibrium and similar in patients and controls (genotypes BB, Bb, and bb: 22.0%, 38.5%, and 39.5% in patients versus 24.7%, 48.2%, and 27.1% in controls). There were statistically significant differences in Hct, Hb level, EPO dose, and EPO-Hb ratio in patients with the three BsmI genotypes, whereas the other parameters were the same. Comparison of patients with an Hb level less than versus greater than 11 g/dL showed that the former patients had lower albumin levels (P = 0.001), higher C-reactive protein levels (P = 0.014), and a greater frequency of BB genotype (P < 0.001). Similarly, comparison of patients with an EPO-Hb ratio in the highest quartile versus those in the lowest quartile showed that the former patients had lower albumin and transferrin levels (P = 0.013 for both) and greater frequencies of BB genotype (P = 0.016). In logistic regression analysis, both BB genotype and low serum albumin level were found to be the only independent predictors for an Hb level less than 11 g/dL (P < 0.001 and P = 0.046, respectively). Both parameters also predicted being in the highest quartile of EPO-Hb ratio (P = 0.004 for both).


CONCLUSIONS
The VDR BsmI gene polymorphism may predict both Hb level and EPO need in HD patients. However, because the underlying mechanisms have not been clarified in the present study, further research on this issue is needed.
D000328:Adult; D000740:Anemia / Q000235:genetics* / Q000517:prevention & control*; D004334:Drug Administration Schedule; D004911:Erythrocyte Volume / Q000235:genetics; D004921:Erythropoietin / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use; D005260:Female; D005838:Genotype; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics / Q000502:physiology; D018167:Receptors, Calcitriol / Q000235:genetics* / Q000502:physiology; D006435:Renal Dialysis / Q000009:adverse effects* / Q000379:methods
D006454:Hemoglobins; D018167:Receptors, Calcitriol; D004921:Erythropoietin