Type I collagen triple helix is composed of heterotrimer of two identical a1 chains and one a2 chain. Procollagen molecule is synthesized inside cells followed by post-translational modifications and then assemblies into triple helix procollagen with diameter of 1.5 nm and length of 300 nm. Then it is secreted to extracellular space by secretory vesicles and further processed by different proteinases. In vitro, collagen fibrils are formed by self-assembly into cross-striated fibrils with the characteristic D-period of 67 nm. In natural bone tissues, collagen fibrils are the scaffold for biomineralization. It is believed that collagen molecules are secreted as amorphous and non-crystalline forms and then transformed into crystalline forms gradually. Mg-based alloys have promising future for orthopedic applications with respect to their mechanical properties, degradation properties, and biocompatibility.

While the exact mechanism of collagen fibril formation on Mg surface in vivo remains unknown, in vitro self-assembly model established in this work provides a simple and alternative way to study how Mg materials interact with collagen molecules. Collagen fibril formation on mica surface involves the adsorption of collagen molecules, surface diffusion, nucleation of fibrils and fibril elongation. A lot of studies have shown that collagen could self-assembly into axially aligned fibrils with Dperiod similar to native bone tissues. However, the assembly of collagen on mica surface could be different from that on Mg-alloy surface due to their distinct surface characteristics and electrostatics. Once in contact with body fluid, the metal elements in Mg materials will be oxidized into metal cations followed by the formation of a layer of metal hydroxide. Postulate such an effect if we take into account the study by Lewington et al. in which a decrease in 2 mmHg was shown to be associated with a 7% and a 10% reduction in CAD and stroke mortality, respectively. Further, in our study the effects on SBP associated with the SNPs studied were within the range of values shown to produce positive changes in cardiovascular disease and stroke risk in populations.

Some studies have shown small genetic effects on SBP that would be difficult to detect in the clinic. However, in our study we observed effects in the range of 6 to 14 mmHg; values that would have an effect at the individual level and, as such, would warrant further prospective studies. For instance, it is estimated that in patients with stage 1 hypertension with at least one additional cardiovascular disease risk factor, achieving a sustained 12 mmHg reduction in SBP over 10 years will prevent 1 death for every 11 patients treated. One limitation of our study is that the associations described apply only to a white Caucasian population. Given the well-documented differences in incidence of hypertension in LY2835219 company various ethnic groups and the significantly different allele distributions at some SNP markers between major ethnic groups, new studies in other populations should be performed to ascertain whether our results can be generalized. In addition, sample size is always an issue to be considered in association studies. Hence, bigger sample sizes or other hypertensive populations would be necessary to corroborate these findings.