The Relationship Between Polymorphisms In Plastin 3 Gene And Osteoporotic Fracture Risk Or Bone Mineral Density In Postmenopausal Chinese Women

Aims: The Plastin 3(PLS3) gene is located on the X chromosome and encodes the actin-binding protein plastin 3, which is responsible for the dynamic assembly and disassembly of the actin cytoskeleton. Mutations in PLS3 were identified to be associated with osteoporosis and fractures in the Rotterdam study(RS) population. We studied whether PLS3 polymorphisms are associated with the risk of osteoporotic fractures or low bone mineral density(BMD) in postmenopausal Chinese women. Methods: A total of 3,661 unrelated postmenopausal women were recruited, including 1,083 patients with osteoporotic fractures and 2,578 healthy controls. Six tagging SNPs in PLS3 and one identified genetic risk factor for osteoporosis in the RS population(rs140121121) were genotyped in all participants. BMD values at the lumbar spine(L1-4), femoral neck and total hip were measured in 3,166 subjects. Results: The rs140121121 SNP was not found in any of the participants. In addition, after Bonferroni correction, there was no polymorphism of PLS3 gene found to be associated with osteoporotic fractures or BMD in postmenopausal Chinese women. Conclusion: Our results suggest that PLS3 polymorphisms aren’t associated with the risk of osteoporotic fractures or BMD in postmenopausal Chinese women. The PLS3 genetic risk factors for osteoporotic fractures and low BMD are therefore not identical across populations with distinct ethnic backgrounds.Aims: We aimed to analyze the clinical manifestations to identify the disease-causing mutations in Chinese hypophosphatasia patients, and help people realize the racial difference between diversified ethnic groups.Methods: In family 1, a 35 year-old nonconsanguineous male was the proband with the severe clinical manifestation of hypophosphatasia, his mother displayed mild clinical symptoms. In family 2, the proband was a 5-year-old boy, and his consanguineous parents had no abnormal sign. All 12 exons and the exon-intron boundaries of the ALPL gene were amplified and directly sequenced in two probands from two unrelated Chinese families. The mutation sites were identified in other unaffected members of these two families and 200 healthy controls. Results: In family 1, one novel missense mutation c.532T>C which consisted of a heterozygous T>C transition at nucleotide 532 in exon 6 was detected in the proband and his mother. In family 2, the proband revealed two missense mutations in exon 4 and exon 9 respectively, the one in exon 4 was a novel mutation(c.269A>G) which resulted in p.Asp90 Gly in the mature ALPL polypeptide. Another mutation was c.871G> A in exon 9, which had been already reported in 1998. His mother was a health carrier who harbored the same missense mutation in exon 4 without any clinical manifestations. Conclusions: Our study showed that two novel mutations of the ALPL gene c.532T>C in exon 6 and c.269A>G in exon 4, take responsibility for hypophosphatasia in Chinese patients.