Introduction: Osteoporosis is a common skeletal disease characterized by a combination of low bone mass and altered bone microarchitecture with a consequent increase of fragility. The human CER1 is a novel candidate gene for osteoporosis that can bind directly to bone morphogenetic proteins and inhibit their activity. In this study we evaluated the contribution of five novel gene single-nucleotide polymorphisms (SNPs) of CER1 in blood samples from osteoporotic and control groups.

Materials and Methods: Peripheral blood samples from 100 postmenopausal women with osteoporosis and 50 healthy Greek women, between 45 and 85 years of age, were collected and DNA was extracted. CER1 polymorphisms genotyping was carried out by PCR and sequencing of the whole gene. Bone mineral density (BMD) was examined by DXA. Statistical analysis was performed using Pearson χ2 or Fisher’s exact test in order to compare allelic frequency distribution.

Results: Genetic analysis of the CER1 gene revealed five SNPs at the positions 239C> G (rs3747532), 1058G> T (rs1494360), 2160A> G, 2355A> G (rs17289263), and 2749T> C of the CER1 gene. The above genotypes were distributed differently among osteoporotic and controls. In osteoporotic patients, the SNPs frequencies were: 78.6% heterozygotes and 3.6% homozygotes for 239C> G SNP, 66.7% and 4.3% heterozygotes and homozygotes, respectively, with T allele at the position 1058, 52.4% heterozygotes and 9.5% homozygotes for the polymorphic site A> G nt.2160, 51.2% heterozygotes and 2.4% homozygotes for the G allele at 2355 position of the CER1 gene, whereas only heterozygotes (38.9%) for the 2749T> C polymorphic site were determined (P< 0.001). However, in the control group the polymorphisms were detected only in heterozygosity and the overall distributions of the polymorphisms 239C> G, 1058G> T, 2160A> G, 2355A-> G, and 2749T> C, were 38.9%, 31.3%, 15.6%, 9.4%, 6.9% (P< 0.001), respectively.

Discussion: All the above polymorphisms, except the SNP rs3747532, are correlated with osteoporotic patients for the first time. Allele frequencies of the control group are significantly lower than those of osteoporotic for any of the five polymorphisms. These data provide the first evidence of an association (and most possible significant cumulative contribution) between the aforementioned genotypes in CER1 gene and the risk for osteoporosis in postmenopausal women.