Genetic Epidemiological Study On The Association Of Vitamin D Binding Protein Variants With Serum Vitamin D And Hypertension

Objectives Vitamin D plays an important role in skeletal and cardiovascular health.Vitamin D-binding protein (DBP) plays a biological effect by binding to vitamin Dmetabolites and transporting them to target tissues. We aimed to investigate theassociation of common genetic variants in DBP with serum vitamin D, blood pressureand hypertension in Chinese.Methods We invited1,643unrelated employees and retired workers of a factory inDali (25°N) to participate from March to May,2010, and1203participants wereincluded in the present analysis. We administered a standardized questionnaire tocollect information on demographic information, medical history, and the use ofmedications. We also performed anthropometric measurements, including body height,body weight, waist and hip circumferences. Radioimmunoassay was used to detectserum levels of25(OH)D. DBP variants were genotyped using SNaPshot method.Vitamin D deficiency was defined as a serum25(OH)D <50nmol/L.Results1. One thousand two hundred and three participants, with a mean concentration ofserum25(OH)D57.4nmol/L, included469participants (39%) with vitamin Ddeficiency. Women compared with men had significantly higher prevalence ofvitamin D deficiency (46.3vs.34.6%，P<0.0001). Participants with normal serum25(OH)D compared with patients with vitamin D deficiency had a significantlylower systolic blood pressure (126.7±18.7vs.129.3±22.6, P<0.05) and pulsepressure (47.1±11.8vs.49.6±15.6, P<0.05) in unadjusted analysis. 2. The genotype frequencies of the three SNPs (rs2282679, rs4588, rs7041) in DBPdid not deviate from the Hardy-Weinberg equilibrium. Their genotypes and allelefrequencies were significantly different (P<0.05) between the presence andabsence of vitamin D deficiency. There was significant difference in serum25(OH)D between genotypes in each DBP variant (rs2282679, rs4588, and rs7041)both before and after adjusted for confounding factors (P<0.05). The homozygotesof rs2282679CC, rs4588AA, and rs7041TT was significantly associated withlower serum levels of25(OH)D, respectively. The DBP-rs2282679and rs4588,but not rs7041, were significantly associated with the presence of vitamin Ddeficiency after adjusted for confounding factors (P<0.05). Linkagedisequilibrium analysis in three locus indicated that DBP-rs4588and rs2282679were in strong LD (r2=0.96), while rs7041was in modest LD with rs4588(r2=0.16) and rs2282679(r2=0.15). DBP-rs4588and rs7041constituted a haploid,which including nine haplotypes. Serum levels of25(OH)D in haplotype GC2-2(rs7041TT and rs4588AA) was significantly lower (P<0.0001), compared withthe haplotype which contains at least one copy of GC1allele.3. Serum25(OH)D was negatively associated with systolic blood pressure (r=-0.070,P=0.015) and pulse pressure (r=-0.102, P<0.001) in Pearson correlation analyses.However, there was no significant difference in systolic or diastolic bloodpressure or pulse pressure between genotypes of DBP-rs2282679, rs4588, rs7041in unadjusted and adjusted analyses (P>0.05). In addition, DBP variants were notassociated with the prevalent hypertension in Chinese either (P>0.05).Conclusions1. Vitamin D deficiency is common in adult population in Dali.2. DBP-rs4588, rs7041, and rs2282679are significantly associated with serum25(OH)D and the presence of vitamin D deficiency;3. DBP-rs4588, rs7041, and rs2282679are not associated with blood pressure or theprevalent hypertension in Chinese.