Bone Fracture History and Prospective Bone Fracture Risk of Hemodialysis Patients are Related to Apolipoprotein E Genotype

Abstract

This investigation of 219 hemodialysis patients relates the history and prospective risk of bone fractures to apolipoprotein E (apoE) genotype. A greater percentage of the 41 patients with the E3/4 and E4/4 genotypes than of the 38 patients with the E2/3 and E2/2 genotypes had a history of bone fractures at the time of recruitment (44% versus 16%, P < 0.005). During the 4 years following recruitment, more of the patients with apoE genotypes E3/4 and E4/4 than with apoE genotypes E2/3 and E2/2 suffered bone fractures, but this difference was not statistically significant (17.1 versus 5.3%, P < 0.1). ApoE genotype appears to be an important genetic risk factor for bone fracture, possibly due to its previously reported influence on vitamin K concentrations in blood.

Ethnic differences in osteocalcin γ-carboxylation, plasma phylloquinone (vitamin K1) and apolipoprotein E genotype

“…In our study, there were no associations between apoE genotype and plasma phylloquinone, in contrast to that previously described in hemodialysis patients (Saupe et al, 1993;Kohlmeier et al, 1998). This difference may be due to several factors including the greater range and lower intrasubject variance of plasma phylloquinone in these patients, their more controlled diet and presence of hyperlipidaemia in some patients Kohlmeier et al, 1998).…”

“…This difference may be due to several factors including the greater range and lower intrasubject variance of plasma phylloquinone in these patients, their more controlled diet and presence of hyperlipidaemia in some patients Kohlmeier et al, 1998). Our study does not demonstrate that the influence of apoE on osteocalcin g-carboxylation was mediated via its influence on plasma phylloquinone.…”

“…Previous studies have shown that circulating phylloquinone concentrations in hemodialysis patients followed the order of apoE24E34E4 (Saupe et al, 1993). It was postulated that this reflected apoE isoform-dependent clearance of phylloquinone-rich remnant lipoproteins by the liver in the order apoE44E34E2, which has been well established for retinyl ester-labelled remnants and may result in more phylloquinone richlipoprotein being available for uptake by bone in subjects with apoE2 (Saupe et al, 1993;Kohlmeier et al, 1998). However, in our study, apoE4 allele was not associated with an increase in adjusted ucOC.…”

“…The apoE gene is polymorphic, with three common alleles resulting in six genotypes (E2/2, E2/3, E2/4, E3/3, E3/4 and E4/4) (Davignon et al, 1988). ApoE genotype has been linked to the TRL-mediated transport of phylloquinone to bone (Saupe et al, 1993;Kohlmeier et al, 1997) and to osteoporotic fracture risk (Kohlmeier et al, 1998;Cauley et al, 1999) and low BMD (Shiraki et al, 1997), although not all studies find associations between apoE genotype and BMD or fracture risk (Booth et al, 2000, Heikkinen et al, 2000.…”

The Uptake of Lipoprotein-Borne Phylloquinone (Vitamin K1) by Osteoblasts and Osteoblast-Like Cells: Role of Heparan Sulfate Proteoglycans and Apolipoprotein E

“…(11,33) The evidence from our study that apoE has a role in osteoblast uptake of lipoprotein-borne vitamin K is consistent with recent evidence linking apoE polymorphism, vitamin K status, and bone health. (5-8,34 -40) An original report that apoE4 was associated with an increase in self-reported fractures in hemodialysis patients (39) has been confirmed in a prospective study in healthy, elderly white women (40) and a study in Japanese women showed that the apoE4 allele was associated with a reduced bone mineral density (BMD). (38) Our findings suggest the possibility that an enhanced uptake of TRL-vitamin K may be a general property of apoE4-secreting cells but that in vivo this results in an increased hepatic uptake, which has a sparing effect on the availability of vitamin K to bone.…”