Vitamin D receptor (VDR) polymorphisms are associated to spontaneous preterm birth and maternal aspects.

Preterm birth (PTB) is featured by less than 37weeks of gestational age or fewer than 259days since the first day from the last menstrual period. Complications of PTB are the major cause of neonatal deaths, several factors are linked to PTB increased risk including immunological and genetics. Vitamin D plays an important role in immune response modulation and its action occurs through the vitamin D receptor (VDR), which recently has been described as overexpressed in human placenta during the pregnancy. Herein we assessed two single nucleotide polymorphisms (SNPs) FokI (rs2228570 A>G) and Cdx-2 (rs11568820 T>C), within VDR, using TaqMan fluorogenic probes, and differential susceptibility to SPTB. We assessed 104 pregnant women with SPTB and 85 women with normal birth in a Northeastern Brazilian population. Statistically significant differences for both SNPs where found when comparing allele and genotype frequencies in both groups: the T allele for rs2228570 and A allele for rs11568820 were significantly more frequent in SPTB group than in normal birth group (p=0.000013 and p=0.00466, respectively). The rs11568820 A/A genotype was associated to clinical/demographic variables such as: premature birth (p=0.007), neonate weight (p=0.039), presence of infection during pregnancy (p=0.011) and premature birth among multiparous (p=0.015). The rs2228570 T/T genotype associated with gestational diabetes mellitus (p=0.044) and chorioamnionitis during pregnancy (p=0.043). In conclusion our findings indicate an association between polymorphisms FokI and Cdx-2 within VDR gene and SPTB, suggesting their involvement in the triggering of these syndromes.

Polymorphisms in key bone modulator cytokines genes influence bisphosphonates therapy in postmenopausal women.

Osteoporosis is a multifactorial and debilitating disease resulting from decreased bone mineral density (BMD) and loss of tissue microarchitecture. Ineffective therapies may lead to bone fractures and subsequent death. Single nucleotide polymorphisms (SNPs) in key immune regulator genes have been associated with therapeutic response to bisphosphonates, which are the first therapeutic line of choice for osteoporosis. However, cytokine pathways and their relation with therapeutic adhesion remain to be fully elucidated. Aimed at better understanding these processes, we investigated the response to bisphosphonate therapy in postmenopausal women and four SNPs in key proinflammatory cytokines genes: IL23R +2284 (C>A) (rs10889677), IL17A +672 (G>A) (rs7747909), IL12B +1188 (T>G) (rs3212227) and INF-γ -1616 (G>A) (rs2069705). A total of 69 patients treated with bisphosphonate were followed for a period of 1 up to 4 years, genotyped and compared according to their changes in bone mineral density (BMD) and level of biochemical markers during their treatment. The INF-γ -1616 G/G associated with increased BMD values in femoral neck (GG/AA, p = 0.016) and decreased BMD values in total hip (GG/GA, p = 0.019; GG/AA, p = 0.011). In relation to biochemical markers, INF-γ -1616 SNP associated with increased alkaline phosphatase (GG/AA; p < 0.0001) and parathyroid hormone levels (AA/GA; p = 0.017). Vitamin D values changes were related to IL17A +672 (GG/GA, p = 0.034) and to IL12B +1188 (TT/TG, p = 0.046) SNPs. Besides, significant differences in changes of calcium levels correlated with IL23R +2284 (CC/CA, p = 0.016) genotypes. Altogether, we suggest that these polymorphisms may play an important role for therapeutic decisions in osteoporosis treatment.