Association of Polymorphisms in RANK and RANKL Genes with Osteopenia in Arab Postmenopausal Women

The RANKL/RANK/OPG pathway regulates bone remodelling and turnover. However, the genetic background of bone mineral density (BMD) and osteopenia in Saudi postmenopausal women is yet to be studied. We studied the genetic polymorphism of RANKL/RANK/OPG with BMD and other associated factors in Saudi postmenopausal osteopenic women. A total of 439 (223 osteopenia and 216 control) postmenopausal women were recruited from the orthopaedic department of the King Khalid University Hospital, Riyadh, KSA. Genetic variants of RANK (rs1805034 and rs35211496), RANKL (rs2277438 and rs9533156), and OPG (rs2073618 and rs3102735) were genotyped using RT-PCR. Anthropometrics, bone mineral density, and other bone markers were measured. The levels of bone turnover markers, PTH, and RANKL were found to be significantly different between control and the osteopenia group. The odds ratio of 2.37 (1.00–5.69) for RANK SNP (rs1805034) indicates that subjects with CC genotype are more vulnerable to developing osteopenia as compared to subjects with TT genotype. Similarly, for RANKL SNP (rs2277438), the significant odds ratio of 20.56 (9.82–43.06) indicates that the subjects with GG genotype are at significantly higher risk of having osteopenia compared with the AA genotype subjects. In addition, G allele in rs2277438 also found to be a risk factor for osteopenia 4.54 (3.18–6.49) compared with A allele. However, none of the OPG genotypes shows association with osteopenia. The association of RANK polymorphisms with osteopenia shows its clinical importance in the diagnosis and prognosis of the bone diseases; here, we suggest that the subjects with RANK and RANKL polymorphisms may develop osteoporosis.