LAUSR

Abstract Vitamin D binding protein (DBP) is one of regulators of vitamin D serum levels. rs4588 and rs7041 polymorphisms of the DBP gene constitute the genetic basis of the three major isoforms of circulating DBP, called GC1s, GC1f and GC2. We evaluated the association between the rs4588, rs7041, rs2282679 SNPs and of DBP isoforms with DBP and 25(OH)D serum levels and investigated whether these gene variants influence on the presence of vitamin D deficiency in a non-selected women sample. In this cross-sectional study, bio-repository samples of 443 apparently healthy women aged 20 to 72 years were analyzed. Most of the participants were ppostmenopausal (n=359). Sufficient circulating levels of 25(OH)D was considered as ≥20ng/mL and deficiency as <20ng/mL. Clinical and biochemical profile were collected. Participants were genotyped for rs4588, rs7041, and rs2282679 polymorphisms by RT-PCR. BDP isoforms were constructed from the combination of the rs4588 and rs7041 polymorphisms, where GC1s= rs4588CC and rs7041GG; GC1f= rs4588CC and rs7041TT and Gc2= rs4588AA and rs7041TT. Mean age and BMI were 53.4±9.4 years and 27.8±5.8, respectively. 25(OH)D levels in total sample was 22.8±8.3ng/mL and 60% had adequate circulating 25(OH)D levels. rs4588, rs2282679 SNPs and the GC2 isoforms were associated with lower DBP levels (rs4588: CC=203.0±28.3; CA=196.5±29.9; AA=184.0±36.9; linear p trend<0.001, B=-8.4; rs2282679: AA=203.1±27.9; AC=196.4±30.0; CC=180.9±38.2; linear p trend<0.001, B=-9.3; and DBP isoforms: GC1s=199.4±29.9; GC1f=204.8±31.6; GC2=180.8±37.6; linear p trend=0.012, B=-7.7) and rs2282689 as well as GC2 isoform were associated with lower 25(OH)D levels (rs2282679: AA=23.4±8.8; AC=22.8±7.8; CC=19.7±7.2; linear p trend=0.034, B=-1.3; and DBP isoforms: GC1s=23.8±9.2; GC1f=20.6±8.3; GC2=20.3±7.4; linear p trend=0.015, B=-1.9). CC genotype of rs2282679 (PR 1.74; 95%CI 1.30;2.24; p<0.001), GC2 isoform (PR 1.66; 95%CI 1.17; 2.38; p=0.005), time since menopause (PR 1.02; 95%CI 1.003;1.03, p= 0.016) and HOMA-IR (PR 1.02; 95%CI 1.01;1.03, p= 0.004) were associated with higher prevalence ratios for 25(OH)D deficiency. DBP levels (per 30 ug/mL of DBP increase, PR 0.89; 95%CI 0.80;0.99; p=0.027) were related to lower prevalence ratios for 25(OH)D deficiency. Except for HOMA-IR, these PR remained significant after adjustment for age and BMI. In conclusion, the present results suggest that rs2282679 and the GC2 isoform of DBP are related to lower DBP serum levels and with the susceptibility to 25(OH)D deficiency in adult and postmenopausal women. Support: CNPq, FAPERGS and FIPE/HCPA