Polymorphisms in the estrogen receptor genes are associated with hip fractures in Chinese

Hip fractures (HF) are a major cause of public health burden with strong genetic determination. However, the true causal genes remain largely unknown.

Based on the important biological role of estrogens in bone homeostasis, this study aimed to investigate whether the estrogen receptor genes, ESR1 and ESR2, affect the onset of HF in 700 elderly Chinese subjects (350 with osteoporotic HF and 350 healthy controls). We genotyped 32 SNPs in total and examined their associations both by the single-SNP and haplotype tests.

We identified two novel SNPs of ESR1, rs3020314 and rs1884051, were significantly associated with HF (rs3020314: P=0.0004, OR=1.66, 95%CI: 1.25-2.18; rs1884051: P=0.0004, OR=1.46, 95%CI: 1.19-1.81). We firstly detected significant association of ESR2 with HF (rs960070: P=0.0070, OR=1.43, 95%CI: 1.10-1.86). Haplotype analyses corroborated our single-SNP results.

Our findings have important implications for understanding the pathology of osteoporotic fractures. Independent replication studies are needed to validate our results and explore the most possible functional variants for molecular studies.