Association and haplotype analyses of the COL1A2 and ER-α gene polymorphisms with bone size and height in Chinese

Abstract Bone size (BS) is another risk factor of fracture independent of BMD in determining bone strength, and height is highly related with BS. To test the effect of the estrogen receptor-α (ER-α) and collagen type I α 2 (COL1A2) genes on the variation of BS and height, we genotyped the Pvu II and Xba I polymorphisms in the intron 1 of the ER-α gene and the Msp I and ( GT ) n markers in the intron 47 and intron 1 of the COL1A2 gene in 400 Chinese nuclear families with a total of 1256 individuals. The BS at the hip and spine was measured using a Hologic QDR 2000 dual-energy X-ray absorptiometry (DXA) scanner. Population stratification, total-family association, and within-family association were used to test the relationship of BS (at the spine and hip) and height with the four polymorphisms. We also performed these association analyses with the haplotypes of the Msp I and ( GT ) n polymorphisms in the COL1A2 gene, and with the haplotypes of the Pvu II and Xba I markers in the ER-α gene. Weak within-family association was found between the COL1A2- Msp I ( P = 0.05) and the femoral neck BS, between the ER-α- PX ( P = 0.04) and the intertrochanter BS, and between the COL1A2-( GT ) 1 7 ( P = 0.02), COL1A2- m ( GT ) 17 ( P = 0.009) and height. Subsequent permutation tests generally confirmed the suggestive within-family association. For the weak within-family association, the proportions of phenotypic variance accounted by the COL1A2- Msp I, ER-α- PX , COL1A2-( GT ) 1 7 , COL1A2- m ( GT ) 17 markers were 1.50%, 1.51%, 2.15%, and 2.43% for the corresponding phenotypes. The association results indicate that the ( GT ) n and Msp I markers of COL1A2 gene may have some influence on the variation of both BS and height, and the Xba I and Pvu II markers of ER-α gene may have some effect on the variation of height in Chinese but not on the variation of BS.