A number of single nucleotide polymorphisms (SNPs) related to height have been detected. Calcium metabolism is important for the skeleton and accordingly also for adult height. Therefore, in the present study, nine SNPs related to the vitamin D receptor (VDR) gene and serum levels of 25-hydroxyvitamin D (25(OH)D), calcium, phosphate and parathyroid hormone (PTH) were related to height in 9471 subjects. Relation with height was evaluated with linear regression for trend across SNP genotypes with age and gender as covariates. After correcting for multiple testing, significant associations with height were found for two SNPs related to the VDR gene (rs1544410 (Bsml) and rs7975232 (Apal)), one SNP related to serum 25(OH)D (rs3829251 at the DHCR7/NADSYN1 gene), one SNP related to serum calcium (rs1459015 at the PTH gene) and one SNP related to serum phosphate (rs1697421 at the ALPL gene). For rs3829251, the mean differences in height between major and minor homozygotes were 1.5-2.0 cm (P
High serum thyrotropin (TSH) levels predict cardiovascular disease (CVD). Recently several single nucleotide polymorphisms (SNPs) associated with TSH levels have been identified, one of them being the rs4704397 SNP in the phosphodiesterase 8B (PDE8B) gene. If the relation between thyroid function and CVD is causal, one could also expect rs4704397 genotypes to predict CVD and possibly health in general.
DNA was prepared and genotyping performed for rs4704397 in subjects who participated in the fourth survey of the Tromsø Study in 1994-1995 and who were registered with the endpoints myocardial infarction (MI), type 2 diabetes (T2DM), cancer, or death, as well as a randomly selected control group. Similarly, genotyping was performed in subjects who had participated in clinical trials where serum TSH, free T4 (fT4), and free T3 (fT3) were measured.
From the Tromsø Study, 8938 subjects without thyroid disease or thyroid medication were successfully genotyped for rs4704397. Among these, 2098 were registered with MI, 1025 with T2DM, 2748 with cancer, and 3592 had died. The minor homozygote genotype (A:A) had a median serum TSH level that was 0.29?mIU/L higher than in the major homozygote genotype (G:G). The A:A genotype had a significantly increased risk of MI as compared to the G:G genotype (1.14 [1.00-1.29], hazard ratio [confidence interval], Cox regression with adjustment for age, sex, and body mass index). No significant associations were seen with the other endpoints or CVD risk factors. Furthermore, subjects with the G:G genotype were significantly taller than subjects with the A:A genotype (mean difference 1.5?cm). In 584 subjects with serum TSH, fT4, and fT3 measurements, the subjects with the A:A genotype had significantly higher serum TSH and nonsignificantly lower serum fT3 (mean difference 0.15?pmol/L) levels than subjects with the G:G genotype.
rs4704397 is associated with thyroid function, risk of MI, and body height. However, confirmation in other cohorts is needed before firm conclusions can be drawn.