Association between NF-κB Signal Pathway-Related Gene Polymorphisms and Response to Alendronate Treatment in Postmenopausal Chinese Women with Low Bone Mineral Density.

Background: Osteoporosis is a systemic bone disease characterized by reduction of bone content. Bisphosphonates are first-line treatments for osteoporosis, but they have variable effectiveness. Genetic factors may explain these differences. The NF-κB signaling pathway plays a key role in the regulation of bone metabolism. We aimed to determine whether genetic variations in the NF-κB signaling pathway affect the effectiveness of alendronate in postmenopausal Chinese women with low bone mass. Methods: We recruited 455 postmenopausal Han Chinese women with primary osteoporosis or osteopenia aged 48-90 yrs who had experienced no spontaneous menses for at least 1 yr. All participants had dual X-ray absorptiometry (DEXA) bone mineral density (BMD) measurement at baseline and 1 yr after treatment. Treatment involved 1 yr administration of 70 mg oral alendronate weekly and 600 mg calcium and 125 IU of vitamin D daily. Thirteen tagSNPs in NF-κB1 (rs28362491, rs3774937, rs230521, rs230510, and rs4648068), RELA (rs7119750, rs11820062), and NLRC5 (rs289747, rs1566439, rs1684575, rs289726, rs289723, and rs41383) were chosen from the NCBI Locus Link and HapMap and genotyped individually. Genetic variation in these genes and the corresponding therapeutic response to alendronate treatment were analyzed. Results: Among the 13 tagSNPs, rs289747 was significantly correlated with the BMD change rate at the femoral neck (P=0.048). This significance no longer existed after Bonferroni correction. We then performed principal component analysis (PCA) and found NLRC5 (rs289747 and rs1566439) were strongly correlated with alendronate efficacy in femoral phenotypes and were major components of BMD change values, particularly total hip and intertrochanteric phenotypes. Furthermore, the PLINK linear regression GLM model revealed that haplotype TT of RELA (rs7119750 and rs11820062) and ICCTA of NF-κB1 (rs28362491, rs3774937, rs230521, rs230510, and rs4648068) were associated with BMD of the total hip among each haplotype after 1 yr of treatment. Conclusion: The NF-κB1, RELA, and NLRC5 genetic variations affect the therapeutic response of alendronate treatment for postmenopausal osteoporosis.

The responses of serum transferrin receptors to iron supplements in subjects with iron-deficiency erythropoiesis and iron-deficiency anaemia.

We aimed to study the response of serum transferrin receptors (sTfR) to Fe supplementation in women of childbearing age with Fe-deficiency erythropoiesis (IDE) and Fe-deficiency anaemia (IDA). Primary screening was performed in 942 women ranging in age from 18 to 45 years. After Fe-related biochemical indices such as serum ferritin, Zn protoporphyrin and Hb were determined, the subjects were divided into four groups: normal, Fe store depletion, IDE and IDA. A total of 131 women were randomly selected from the normal, IDE and IDA groups. Subsequently, seventy-six women with IDE and IDA were given various doses of Fe (14 mg/d for IDE; 28 mg/d for IDA) with ferrous l-threonate capsules for twelve consecutive weeks. After receiving Fe supplements, the levels of Fe and sTfR were determined at weeks 0, 3, 6, 9 and 12. The levels of sTfR in women of childbearing age with IDE and IDA were significantly higher than those in the normal group. After receiving Fe supplements, the levels of sTfR were significantly decreased in women of childbearing age with IDE and IDA, while the levels of serum ferritin were significantly increased. In conclusion, STfR can be used as a reliable indicator for assessing the efficacy of Fe supplements.

Levels of serum transferrin receptor and its response to Fe-supplement in Fe-deficient children.

The object of the present study was to investigate the levels of serum transferrin receptor (sTfR) and its response to Fe supplementation in Fe-deficient children and the role of sTfR in detecting Fe deficiency and assessing the efficacy of Fe supplementation. According to the diagnostic standard, 1006 children, aged 6-14 years in Fangshan district, Beijing, Peoples Republic of China, were divided into four groups: normal; Fe store depletion (IDs); Fe deficiency erythropoiesis (IDE); Fe deficiency anaemia (IDA). sTfR was determined and transferrin receptor-ferritin (TfR-F) index was calculated in 238 children, sixty-four normal and 174 Fe deficient. Children were administered a NaFeEDTA capsule containing 60 mg Fe once per week for the IDs and IDE groups and three times per week for the IDA group for nine consecutive weeks. The parameters reflecting Fe status and sTfR were determined before and after Fe supplementation. The levels of sTfR and TfR-F index in Fe-deficient children were significantly higher than those in the normal group. The receiver operating characteristic curve showed that sTfR has proper diagnostic efficacy for functional Fe deficiency. After Fe supplementation, the level of sTfR was significantly decreased in children with IDs, but not in children with IDE and IDA, while TfR-F index was significantly decreased in Fe-deficient children. sTfR is a reliable indicator for detecting functional Fe deficiency, and TfR-F index is a sensitive parameter for assessing the efficacy of Fe supplementation.

The maternal combined supplementation of folic acid and Vitamin B(12) suppresses ethanol-induced developmental toxicity in mouse fetuses.

Maternal ethanol consumption during pregnancy can induce developmental defects in the fetus. The objective of this study was to assess whether combined supplementation of folic acid (FA) and Vitamin B(12) (VB(12)) in dams would suppress ethanol-induced developmental toxicity in CD-1 mice. Ethanol (5.0 g/kg) was given intragastrically from gestational day (GD) 6 to GD15. Vitamin supplementation groups were additionally given 60.0 mg/kg FA, 1.0 mg/kg VB(12), or 60.0 mg/kg FA+1.0 mg/kg VB(12) during GD1-16. The control group received distilled water only. Results of litter evaluation on GD18 showed that combined supplementation of FA and VB(12) ameliorated many of the adverse effects of ethanol. In contrast, the single vitamin supplementation groups showed little or no amelioration. These results suggest that combined supplementation of FA and VB(12) was more effective than each vitamin toward suppressing ethanol-induced developmental toxicity in CD-1 mice.

[Iron status and effect of early iron supplementation on sub-clinical iron deficiency in rural school-age children from mountainous areas of Beijing].

OBJECTIVE: To understand iron nutritional status in school-age children, incidence of the sub-clinical iron deficiency (SID) and effect of iron supplementation on SID in the rural school-age children from mountainous areas of Beijing. METHODS: The dietary survey and food frequency questionnaire survey were conducted in 1,012 school children aged 7 - 13 at rural mountainous areas of Fangshan District, Beijing, and their blood samples were collected for analyzing biochemical indicators for iron nutrition. Two hundred and sixty-seven children with IDs (iron deficiency store) and IDE (iron deficiency erythropoiesis), based on screening criteria for iron-deficiency anemia, received an iron supplementation (NaFeEDTA) capsule (containing 60 mg iron element) weekly, and those with IDA (iron deficiency anemia) received NaFeEDTA capsule thrice weekly for nine weeks. Blood biochemical indicators for iron nutrition were determined repeatedly and compared with those before and after the intervention. RESULTS: The daily average intakes of energy, protein, iron and vitamin C in school children of all age groups reached the daily recommended criteria (> 85% of the RNIs), but the proportion of heme in dietary iron constitution was lower. The average blood biochemical indicators for iron nutrition were as follows: serum ferritin (SF) (50.83 +/- 33.09) micro g/L, free erythrocyte protoporphyrin (FEP) (489.44 +/- 219.61) micro g/L, hemoglobin (Hb) (130.57 +/- 10.82) g/L, and the ratio of FEP/Hb (3.83 +/- 1.96), respectively. Incidence of total iron deficiency in rural children was 26.5%, with proportions of iron deficiency (IDs), iron deficiency erythropoiesis (IDE), and iron deficiency anemia (IDA) of 15.5%, 7.1%, and 3.9% respectively. SID accounted for 85.4% of the total iron deficiency, which was 5.8 times as much as IDA. With iron supplementation for 9 weeks, the hematdogical index of iron increased significantly and returned to the normal level. CONCLUSIONS: The incidence of subclinical iron deficiency in the rural school-age children was insidious and should be attached more importance, which was helpful to its early recognition and intervention. Iron supplementation is important for children with SID to prevent and decrease the occurrence of IDA.