Four of the nine
variations occurred in only one individual: c.723G>A (P241P) in exon 3 and rs59390594, rs71583766, and c.2681A>G in the 3′UTR. In addition, two subjects of African descent carried variations rs13312795 and c.2139-2141delTTC, both in the 3′UTR. The subjects with rare variations did not have hypo- or hyperphosphatemia and did not differ in other biochemical and skeletal parameters from the others. The S3I-201 in vivo three selected polymorphisms rs3832879 (c.212-37insC), rs7955866 (c.716C>T, p.T239M) and rs11063112 (c.2185A>T) occurred in four different haplotype and six different diplotype combinations. The combined haplotypes were Haplotype 1 (− CA 58.1%), 2 (− CT 20.8%), 3 (CCA 10.9%), and 4 (− TT 9.8%), and diplotypes were Diplotype 1 − CA/− CA (32.2%), 2 − CA/− TT (16.9%), 3 − CA/− CT (29%) 4 CCA/CCA (14.8%), 5 CCA/− CT (4.9%), and 6 CCA/− TT (2.2%) ( Fig. 2). Variation in rs3832879 (c.212-37insC) genotype correlated with P-Pi concentration (p = 0.033) (Table 3A). However, no association were present after controlling VE-821 cost for age, gender, pubertal stage and S-25(OH)D (p = 0.398). We identified only 716CC and 716CT genotypes in rs7955866 (c.716C>T,
p.T239M). 716CT heterozygotes had significantly lower mean P-PTH levels and higher U-Pi/U-Crea levels than 716CC homozygotes ( Table 3A). These differences remained significant when analyzed with ANCOVA, which yielded a p-value of 0.042 for P-PTH with covariates gender, pubertal stage, S-25(OH)D and calcium intake, and p = 0.038 for U-Pi/U-Crea with covariates age, gender, pubertal stage, P-Pi, S-25(OH)D, and calcium intake. No significant correlation between the rs11063112 (c.2185A>T) genotype and other variables was observed. When analyzed according to diplotypes (Table 3B) S-FGF23 levels did not differ between diplotypes in the primary analysis or after adjustment for S-25(OH)D, P-PTH and calcium intake (r = 0.02, p = 0.84). There was an association between FGF23 diplotype and P-PTH concentrations (ANOVA p = 0.032, Table 3B). After controlling for
age, pubertal stage, S-25(OH)D, date of sampling and calcium intake the difference between FGF23 diplotypes and P-PTH concentrations remained in girls, but disappeared in boys (ANCOVA; p = 0.037 and p = 0.636). Of the 16 children with elevated PTH, 94% had the rs7955866 716CC genotype Liothyronine Sodium and 63% the − CA/− CA diplotype while in the whole study population the corresponding proportions were 78% and 32%. There was a statistically significant difference between the two groups in the distribution of rs7955866 genotypes (p = 0.018) and the distribution of diplotypes (p = 0.006). There was a trend toward association between higher S-25(OH)D and FGF23 genetic variation (P = 0.097) in the whole group which was masked by the gender interaction: in boys, but not in girls, FGF23 gene variation associated with S-25(OH)D concentrations (p = 0.032).