Genetic Analysis And Ethnic Difference Of Bone Geometry

Osteoporosis has become one of the most important diseases with the aging process over the world. Osteoporotic fracture (OF) is the ultimate consequence of osteoporosis. Bone strength as the ultimate measurement of resistance to OF is mainly determined by bone geometry and bone mineral density (BMD). In the past years, most of the researches were focused on the relationships between BMD, which has a high heritability, and osteoporosis or OF. Numerous association researches about BMD and candidate genes were reported. However, the interethnic differences of OF rate can not be explained by the BMD differences among various ethnic groups in some cases. In addition, investigations demonstrated that the bone geometry with high genetic determination was an important predictor to OF risk independent from BMD. The interethnic differences of bone geometry may be responsible for such differences of OF rate to some extent. Then, the differences of bone geometry among various ethnics may be partially attributed to the genetic differences. To date, there are few studies focusing on the contribution of genotype and ethnicity to bone geometry variation in both Chinese Han population and Caucasians. Therefore, the studies about bone geometry will be beneficial to our understanding of osteoporosis comprehensively and aid to the development of predicting and treatment approaches of osteoporosis and OF risk for clinic application.The hip fracture is a type with high incidence. The aims of this research are to compare the difference of femoral neck (FN) bone geometry in Chinese Han population and Caucasians, and to study therelationships of collagen type I alpha 1 (COLIAl) gene and alpha2-HS-glycoprotein (AHSG) gene with the FN bone geometry parameters using the transmission disequilibrium test (TDT) method in the two populations.In this research, we recruited 1, 228 individuals from 400 Chinese Han nuclear families and 605 individuals from 157 Caucasian nuclear families. Each family was composed of parents and at least one healthy offspring aging from 20 to 45 years old. After the obtaining of the individual informations (age, gender, medical history, etal.), the bone phenotypes (BMD and bone size) were measured using the Hologic DXA machines. Then, five bone geometry parameters, which were cross sectional area (CSA), cortical thickness (CT), endocortical diameter (ED), sectional modulus (Z) and breaking ratio (BR), were calculated based on the measured BMD and bone size. The Spl and PC0L2 polymorphisms of COLIAl gene and Sad polymorphism of AHSG gene were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method for all subjects. With the parents group as the random sample, the differences of FN bone geometry between two ethnics were conducted by using ANOCOVA in the SPSS software, taking gender, height and weight as covariates. Relationships of COLIAl (Spl and PC0L2) and AHSG (Sad) gene polymorphisms with five FN bone geometry parameters were performed using QTDT software with TDT method in all of the subjects of each population.We observed that the differences of CT, ED and BR were significant between the elderly Chinese Han population and Caucasians (p=0. 000, 0.003, 0.011, respectively). In the genetic analysis, the Spl polymorphism of COLIAl gene was significant associated with CSA, CT,ED, BR (/fO.0176, 0.0019, 0.0226, 0.0009, respectively) in the within family association analysis, and was significant linked with BR (p=0. 0394) in Caucasians. In Chinese Han population, we found the significant within family association of PC0L2 polymorphism of COLIAl gene with CT and BR (p =0.0117, 0.0078, respectively) . For the Sacl polymorphism of AHSG gene, we found marginal within family associations with CSA and CT, and significant linkage with CT and BR in Caucasians. In conclusion, there were significant differences of FN bone geometry between Chinese Han population and Caucasians, and COLIAl gene was associated with the variation of FN bone geometry in both populations, while the effects of AHSG gene on Chinese Han population may be modest.