绝经后妇女骨质疏松侯选基因ER、IL-6、COLIA1的研究

Candidate genes of osteoporosis(ER,IL-6,COLIA1) in postmenopausal women

目的 骨质疏松是一种多基因疾病 ,本研究目的是探讨绝经后妇女的雌激素受体(ER)、白介素 6 (IL 6 )和Ⅰ型胶原α1(COLIA1)基因多态性与骨密度等指标的关系。方法 用DEXA检测 2 0 5例绝经后妇女的腰椎和股骨颈骨密度 ,用PCR RFLP方法检测ER基因PvuII和XbaⅠ多态性和Ⅰ型胶原α1(COLIA1)基因多态性 ;PCR扩增IL 6基因 3’端非翻译区的多态性区域。结果 ER基因PP、Pp和pp基因型频率分别为 13 7%、5 1 2 %和 35 1% ,pp型的绝经后妇女股骨颈骨密度Z值明显高于Pp型。ER基因XX、Xx和xx基因型分别占 6 8%、2 5 9%和 6 7 3%。XX基因型的妇女虽然停经时间更长 ,但腰椎骨密度仍高于Xx和xx型。发现了D/D、D/E、C/D、C/C和E/E5种IL 6基因型 ,93%以上的绝经后妇女属于D/D和D/E型。在绝经 10年以上的妇女中 ,D/E型的腰椎骨密度明显高于D/D型 ,且前者的体重指数更高。所有样本的COLIA1基因型检测结果都是无突变的纯合子SS。结论 ER基因型中的pp和XX型可能分别对股骨颈和腰椎有保护作用 ;IL 6基因多态性与停经时间较长的绝经后妇女腰椎骨密度有一定关系 ;COLIA1基因型可能不适于评估本地区绝经后妇女骨密度的差异。

Objective\ To investigate the relationships between ER、IL 6 and COLIA1 gene polymorphisms and bone mineral density(BMD) in postmenopausal women. Methods\ BMD were measured by DEXA at lumbar spine and proximal femur in 205 postmenopausal women. Biochemical markers, such as osteocalcin(BGP) and pyridinoline(Pyd) were also measured. The genotypes of ER and COLIA1 were detected by PCR RFLP method. The polymorphic 3′flanking region of the IL 6 gene was studied by PCR. Results\ The ER genotyping was as follow:PP(13 7%),Pp(51 2%) and pp(35 1%); the genotype frequencies of XX, Xx and xx were 6 8%, 25 9% and 67 3%, respectively. Individuals with pp genotype of ER gene showed a higher BMD at femoral neck, and women with XX genotype had higher lumbar spine bone mass compared with those with Xx and xx ones, although they had longer period since menopause. D/D, D/E, C/D, C/C and E/E 5 genotypes of IL 6 gene were found; 93% of them were present as D/D and D/E genotypes. Women of D/E genotype with more than 10 years of menopause had a higher BMD at lumbar spine and higer body mass index as compared with D/D ones. All the samples showed normal wild type homozygotes SS of COLIA1 gene. Conclusion\ pp and XX genotype of ER gene may have protective effects on femoral neck and lumbar spine, respectively. IL 6 gene polymorphism has some relationship with BMD in postmenopausal women with longer period of menopause. COLIA1 gene polymorphism cannot be used to assess the bone mass of postmenopausal Chinese women. The significance of these genetic markers of osteoporosis needs to be studied further in larger samples and in different areas