Association and linkage analysis of COL1A1 and AHSG gene polymorphisms with femoral neck bone geometric parameters in both Caucasian and Chinese nuclear families.
OBJECTIVE
To simultaneously investigate the contribution of the alpha 1 chain of collagen type 1 (COL1A1) and alpha2-HS-glycoprotein (AHSG) genes to the variation of bone geometric parameters in both Caucasians and Chinese.


METHODS
Six hundred and five Caucasian individuals from 157 nuclear families and 1228 Chinese subjects from 400 nuclear families were genotyped at the AHSG-SacI, COL1A1- PCOL2 and Sp1 polymorphisms using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). 5 FN bone geometric parameters were calculated based on bone mineral density and bone area of femoral neck (FN) measured by dual energy X-ray absorptiometry. Population stratification, total family association, within-family association, and linkage tests were performed by the quantitative transmission disequilibrium test program.


RESULTS
The t-test showed the significant differences of all bone geometric phenotypes (except ED) between Caucasians and Chinese in the offspring using both unadjusted and adjusted (by age, height, weight, and gender) data. In Caucasians, we found significant within-family association results between the COL1A1-Sp1 polymorphism (rs1800012) and cross sectional area (CSA), cortical thickness (CT), endocortical diameter (ED), buckling ratio (BR) (P=0.018, 0.002, 0.023, and 0.001, respectively); the COL1A1-Sp1 polymorphism also detected significant linkage with BR (P=0.039). In the population of China, the within-family associations between the COL1A1-PCOL2 polymorphism (rs1107946) and CT, BR were significant (P=0.012 and 0.008, respectively). Furthermore, evidence of linkage were observed between the AHSG-SacI polymorphism (rs4918) and CT, BR (P=0.042 and 0.014, respectively) in Caucasians, but not in Chinese.


CONCLUSIONS
Our results suggest that the COL1A1 gene may have significantly association with bone geometry in both Caucasians and Chinese, and the AHSG gene may be linked to bone geometry in Caucasians, but not in Chinese. This study represents our first efforts on investigating the importance of the COL1A1 and AHSG genes on bone geometry in both Caucasians and Chinese.
Jiang
Hui
H
Laboratory of Molecular and Statistical Genetics and the Key Laboratory of Protein Chemistry and Developmental Biology of the Ministry of Education, College of Life Sciences, Hu-nan Normal University, Changsha 410081, China.
Lei
Shu-Feng
SF
Xiao
Su-Mei
SM
Chen
Yuan
Y
Sun
Xiao
X
Yang
Fang
F
Li
Li-Ming
LM
Wu
Shan
S
Deng
Hong-Wen
HW
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People; D001798:Blood Proteins / Q000235:genetics*; D002681:China / Q000453:epidemiology; D024042:Collagen Type I / Q000235:genetics*; D000090602:Collagen Type I, alpha 1 Chain; D005260:Female; D005272:Femur Neck / Q000033:anatomy & histology*; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009679:Nuclear Family; D011110:Polymorphism, Genetic / Q000235:genetics; D014481:United States / Q000453:epidemiology; D044465:White People; D055815:Young Adult; D060749:alpha-2-HS-Glycoprotein
C556354:AHSG protein, human; D001798:Blood Proteins; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D060749:alpha-2-HS-Glycoprotein