Hypomethylation of <i>Alu</i> Elements in Post-Menopausal Women with Osteoporosis

<div><p>A decrease in genomic methylation commonly occurs in aging cells; however, whether this epigenetic modification leads to age-related phenotypes has not been evaluated. <i>Alu</i> elements are the major interspersed repetitive DNA elements in humans that lose DNA methylation in aging individuals. Alu demethylation in blood cells starts at approximately 40 years of age, and the degree of Alu hypomethylation increases with age. Bone mass is lost with aging, particularly in menopausal women with lower body mass. Consequently, osteoporosis is commonly found in thin postmenopausal women. Here, we correlated the Alu methylation level of blood cells with bone density in 323 postmenopausal women. Alu hypomethylation was associated with advanced age and lower bone mass density, (P<0.05). The association between the Alu methylation level and bone mass was independent of age, body mass, and body fat, with an odds ratio <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0070386#pone.0070386-Antoniades1" target="_blank">[1]</a>  = 0.4316 (0.2087–0.8927). Individuals of the same age with osteopenia, osteoporosis, and a high body mass index have lower Alu methylation levels (P = 0.0005, 0.003, and ≤0.0001, respectively). Finally, when comparing individuals with the same age and body mass, Alu hypomethylation was observed in individuals with lower bone mass (P<0.0001). In conclusion, there are positive correlations between Alu hypomethylation in blood cells and several age-related phenotypes in bone and body fat. Therefore, reduced global methylation may play a role in the systemic senescence process. Further evaluation of Alu hypomethylation may clarify the epigenetic regulation of osteoporosis in post-menopausal women.</p></div

Alu methylation of osteopenia and osteoporosis.

<p>(<b>A</b>) paired age normal (n = 65) and osteopenia (n = 65); (<b>B</b>) paired age normal (n = 35) and osteoporosis (n = 35). N, normal control. ON, osteopenia. OP, osteoporosis. NS, not significant.</p

Alu methylation of osteopenia and osteoporosis.

<p>Normal (n = 52) and combined osteopenia and osteoporosis (n = 63) were paired by age and BMI.</p

Logistic regression analysis when bone mineral density by DEXA (T-score) cut-offs of normal and osteoporosis was the dependent variable and %mC, %mCmC loci, %uCmC loci, %mCuC loci, %uCuC loci, age, BMI, and %body fat were independent variables.

<p>Different levels of significance at <i>P</i>≤0.05.</p

Mean and median of characteristic data and the correlation (r) between %mC and age-related phenotypes among all menopausal subjects.

<p>L, spine region lumbar; ± SE, standard error; r, correlation coefficient; n, number of cases;</p>*<p><i>P</i><0.05,</p>**<p><i>P</i><0.001.</p

Alu methylation of osteopenia and osteoporosis.

<p>Paired age between cases with body mass index (BMI)<25 kg/m² (n = 80) and cases with BMI≥25 kg/m² (n = 80). NS, not significant.</p

Additional file 1: of Low density lipoprotein receptor-related protein 5 gene polymorphisms and osteoporosis in Thai menopausal women

Haplotype blocks distribution in the LRP5 gene of CHB and JPT populations of HapMap generated by Haploview 4.2 program. Each black triangle depicts haplotype blocks. LD is reported as D′. Bright red represents D' = 1 and LOD ≥ 2, blue represents D' = 1 and LOD < 2, pink represents D' < 1, and LOD ≥ 2, and white represents D' < 1 and LOD < 2. The r2 values are shown in blocks. CHB, Han Chinese in Beijing, China; JPT, Japanese in Tokyo, Japan

Mean and median of %mC level, %mCmC loci, %mCuC loci, %uCmC loci, %uCuC loci and %mCuC loci+%uCmC loci among all menopausal subjects.

<p>± SE, standard error; n, number of cases; %mCmC, %hypermethylated loci;</p><p>%uCuC, %hypomethylated loci; %uCmC and %mCuC, %partially methylated loci.</p