Parathyroid Hormone (PTH) Gene And Bone Mineral Density/Content In Chinese

Today, osteoporosis is a major public health threat for over 200 million people in the world. Especially it is a common disorder afflicting old people. Osteoporosis is a complex disease determined by genetic and environmental risk factors or the interaction of them. Low bone mineral density (BMD) and low bone mineral content (BMC) are two of the most important measurable risk factors to the osteoporotic fracture (OF). Both of them are influenced by nutrition, exercise, heredity, hormone level and many other factors. Among these factors hereditary effect on BMD and BMC is most dominant. There are many candidate genes for BMD and BMC variation according to the biologic function on bone absorption and bone formation of corresponding protein products of these genes. Extensive studies have been conducted to reveal the relationship between candidate genes and bone phenotype variation. Our aim is to to detect whether our interested candidate gene is a gene-a quantitative trait locus (QTL) underlying the BMD and BMC variation by using powerful and cotemporary Transmission disequilibrium test (TDT).In this study, we have recruited 1,263 subjects from 402 nuclear families with both healthy parents and at least one daughter, whose ages range from 20 to 45. All the study subjects belong to the Han ethnic group in Shanghai. Genomic DNA was isolated from the blood of all the samples according to the classical phenol-chloroform extraction protocols. BMD (g/ cm2) and BMC (g) of the spine (L1-L4), femoral neck, trochanter,intertrochanteric region, ward' s triangle and total hip were measured by a Hologic QDR 2000+ dual - energy X-ray absorptiometry (DXA) scanner (Hologic Corporation, Waltham MA). Age, weight and height serviced as significant covariates to adjusted the BMD and BMC value were obtained at the same visit when the bone mass was measured. Applying the polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP), we genotyped all the DNA samples. This RFLP of molecular marker inside the candidate gene for parathyroid hormone gene (PTH), lies in the section of one intron among the second and the third exons which contains BstB I RFLP polymorphism. We simultaneously tested linkage and/or association of the PTH gene with BMD and BMC via TDT. We also tested association alone through the conventional analyses of variance (ANOVA). With the TDT, we did not detect any significant results. However, with the ANOVA, significant associations were found in the mother group between the PTH BstB I marker polymorphism and the intertrochanter region BMD (p=0. 020) and BMC (p=0.010), the ward' s triangle BMD (p=0.029) and BMC (p=0. 043), the total hip BMD (p=0. 020) and BMC (p=0. 019). The association detected by the ANOVA may be spurious. Our data do not support the PTH gene' s BstB I polymorphism as a QTL underlying the bone mass variation at the spine and hip in Chinese.