绝经后妇女骨密度与Ⅰ型胶原α_1链及α_2链基因多态性相关性研究

Relationship between Polymorphism of Collagen Type-I Alpha-1 and Alpha-2 Gene and Bone Mineral Density in Postmenopause Women

目的探讨人Ⅰ型胶原α1链(COL1A1)及α2链(COL1A2)基因型与绝经后妇女骨密度相互关系。方法选取年龄≥42岁绝经后妇女(自然绝经≥2年)231例,采用双能X线吸收法(DEXA)测定其全身、腰椎2～4(L2～4)、股骨颈(Neck)、Ward?三角和大转子区等部位的骨密度(BMD)值,并采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测外周血白细胞基因组Ⅰ型胶原α1链及α2链基因型。结果231例受试对象中,Ⅰ型胶原α1链PCR扩增产物未发现ACCB7I酶切位点,SpⅠ结合位点不存在G→T突变,Ⅰ型胶原α1链基因型均为SS型;Ⅰ型胶原α2链基因型分别为EE型113例,Ee型91例,ee型27例(分别占48.9%、39.4%、11.7%),等位基因频率E和e各为68.6%、31.4%。基因型分布符合Hardy-weinberg定律。携带EE基因型的个体比Ee基因型和ee基因型个体的骨密度值为低,但只在腰椎侧位(L2-L4)、股骨颈(Neck)、大转子(Troch)、Ward?s三角(Ward?s)等部位的骨密度值EE基因型比Ee基因型携带者明显降低(P<0.05)。结论广州地区绝经后妇女COL1A1SpⅠ结合位点不存在G→T突变。COL1A2基因EE型个体较Ee基因型及ee基因个体的骨密度值低,绝经后妇女骨密度与COL1A2基因多态性存在一定相关性。

Objective To Investigate the polymorphism of collagen type Ⅰ alpha 1 （COL1A1） and collagen type Ⅰ alpha 2 （COL1A2） gene in Chinese postmenopause women and the relationship between polymorphism of collagen type 1 alpha genes and the bone mineral density （BMD）. Method Polymerase chain reaction-restriction fragment length polymorphism （PCR-BELP） was used to detect the genotypes of COL1A1 and COL1A2 in 231 unrelated postmenopause women. Dual-energy X-ray absorptiometry （DEXA） was used to measure BMD in different parts of the body. These included the total body measurement （Total）, femoral neck （Neck）, lumbar spine （L2-4）, troehanter （Troeh） and ward＇s triangle （Ward＇s）. Result The C→T mutation of COL1A1 was not founded. Neither Ss nor ss genotypes of COL1A1 gene was found in all subjects. The genotypes of all samples in this cohort were type SS. The distribution of COL1A2 genotype is as following： EE, 113 eases, 48.9%; Ee： 91 eases, 39.4%; ee： 27 eases, 11.7%. The frequencies of allele E and e were 68.6% and 31.4%, respectively. The frequencies distribution of EeoR Ⅰalleles followed the Hardy-Weinberg equilibrium. The mean BMD at L2-L4, Neck , Troeh, Ward＇s sites was consistently lower in individuals with EE genotype than with Ee （P〈0.05） by analysis of variance [ANOVA]. Significant difference at Total, Subtot and Inter sites between the two groups was not observed. Significant difference of BMD between the subjects with ee genotype and EE genotype, and ee and Ee genotype was not seen. Conclusion C→T mutation of COL1A1 was not found in postmenopause women in Guangzhou. There is no association between Sp I genotype of COL1A1 gene and BMD. For COL1A2, the subjects with Ee genotype had a higher mean BMD than subjects with EE genotype. COL1A2 EeoR → genetic polymorphism may be associated with the BMD of postmenopause women in Guangzhou.