Influência dos polimorfismos no gene do receptor de vitamina D (VDR) sobre a massa óssea em nutrizes adolescentes

Abstract

In adolescent mothers with low dietary calcium intake, calcium plus vitamin D supplementation during mid-pregnancy appears to protect against excessive maternal bone loss during lactation. Polymorphisms in the vitamin D receptor (VDR) gene have been associated with bone mass in adolescents and it is possible that bone loss of lactation is also influenced by these polymorphisms. Moreover, it is also possible that these polymorphisms are able to modulate bone responses to calcium and vitamin D supplementation. The objective of the study was to evaluate the influence of VDR gene polymorphisms and its interaction with calcium and vitamin D supplementation during pregnancy on bone mass of lactating adolescents (14-19 y) with habitually low calcium intake (~600mg/d). Adolescents received calcium plus vitamin D supplements (600mg+200UI/d; n=30) or placebo (n=26) from 26 wk of gestation until parturition. Serum concentrations of IGF-1, PTH, estradiol, prolactin and 25(OH)D were assessed at 26wk gestation, 5 and 20 wk postpartum. Bone mass assessments included bone mineral content (BMC), density (BMD) and bone area (BA) at total body and specific sites [lumbar spine (LS, L1-L4), total hip (TH) and femoral neck (FN)] assessed by DXA at 5 and 20 wk postpartum. The polymorphisms rs1544410 (G>A), rs10735810 (C>T), rs7975232 (T>G), rs731236 (T>C) were determined by RFLP. Polymorphisms rs7139166 (G>C, 1521pb) and rs4516035 (A>G, 1012pb), located in the gene promoter region, were determined by real-time PCR. The effects of polymorphisms and its interaction with supplementation on bone mass were assessed by ANCOVA after adjustment for significant covariates. The genotype distribution for all polymorphisms evaluated were not different between placebo and supplemented groups. Adolescents with CC (rs10735810) genotype had lower losses in total body BMC from 5 to 20 wk postpartum compared to those with CT and TT genotypes (P <0.01). At femoral neck, lactating adolescents with TC genotype (rs731236) had lower losses in BMD and Z score BMD from 5 to 20 wk postpartum compared to those with CC and TT genotypes (P <0.01). Supplemented mothers with 1521GG/1012AA genotype combination had higher serum PTH at 20 wk postpartum (P=0.02) and greater reduction in total BA from 5 to 20 wk compared to those with the same genotype combination who received placebo (P=0.03). Supplemented mothers with 1521GG/1012AA had lower reduction at total Z score BMD (P=0.03) and femoral neck BMD (P=0.008) and higher increment at total hip BA (P = 0.05) from 5 to 20 wk postpartum compared to those supplemented mothers with other genotype combinations, and to mothers with 1521GG/1012AA who received placebo. Overall, our results suggest that VDR gene polymorphisms, especially those located at promoter region, may influence bone mass during lactation as well as maternal bone responses to calcium and vitamin D supplementation during pregnancy in adolescents