GC、CYP2R1基因多态性与北京汉族绝经后妇女血清维生素D水平的关系

【作者】 徐雯；

【导师】 夏维波； 李梅； 聂敏； 姜艳；

【作者基本信息】 北京协和医学院 ， 临床医学， 2012， 博士

【摘要】 目的：维生素D缺乏是一个普遍而重要的健康问题,近期研究发现遗传因素对血清25(OH)D水平有一定影响。本研究的目的是探讨GC及CYP2R1基因多态性与维生素D水平的关系,并探讨GC基因多态性与骨密度、骨转换标志物及骨量异常、骨折、椎体骨折的关系。方法：以北京地区随机抽样的1494名汉族绝经后妇女为研究对象,通过问卷调查和胸腰椎X线检查确定自报骨折及椎体骨折表型。以双能X线吸收仪检测腰椎(L2-4)、股骨颈和全髋三个部位的骨密度,用罗氏自动检测仪通过电化学发光免疫测定法检测样本血清的β-CTX、P1NP和25(OH)D水平。通过TaqMan基因分型技术获得GC和CYP2R1基因6个SNP位点的基因型。采用线性回归、二元logistic回归等统计学方法分析各SNP位点基因型和单体型与血清25(OH)D水平、骨密度、骨转换标志物及骨量异常、骨折、椎体骨折的关系。结果：1.本研究的1494例研究对象中有维生素D缺乏的1338人,维生素D相对不足的146人,分别占总研究对象的89.6%和9.8%。2.GC基因rs222020位点(P=0.003)和rs2298849位点(P＝3.73e-4)的多态性与血清25(OH)D水平显著相关,并且这种显著性经过对多重检验的校正后仍然存在。rs222020的少见等位基因C和rs2298849的少见等位基因G可能是血清25(OH)D水平的保护性等位基因。rs222020-rs2298849的单体型CG对应升高的血清25(OH)D水平(p=0.138,P＝0.001),单体型TA对应降低的血清25(OH)D水平(β=-0.118,P＝0.002)。3. CYP2R1基因多态性与血清25(OH)D水平无显著相关性。4.GC基因多态性与β-CTX、P1NP和腰椎L2-4、股骨颈、全髋各部位骨密度及骨量异常风险、脆性骨折风险、有X证据的椎体骨折风险无显著相关性。CYP2R1基因多态性与β-CTX、P1NP水平有显著相关性,与上述各部位骨密度及骨量异常风险、骨折风险无显著相关性。结论：在北京汉族绝经后妇女群体中,GC基因的多态性与血清25(OH)D水平显著相关,CYP2R1基因多态性与血清25(OH)D水平无显著相关性。CYP2R1基因与β-CTX、P1NP水平的相关性需要进一步验证。更多还原

【Abstract】 Objective:Vitamin D deficiency is a common and important healthy problem. Recently people have found some genetic factors that may influence serum25(OH)D concentration. The aim of our study is to determine if GC and CYP2R1genetic variants have association with serum25(OH)D level and to explore if there is association between GC variants and bone mineral density (BMD), bone turnover markers, fracture, or vertebral fracture in postmenopausal women.Methods:We randomly selected a population of1494postmenopausal women of Han ethnic group from7communities in Beijing. Main information was acquired as follows: Osteoporotic fracture and vertebral fracture phenotypes:questionnaire and vertebral X-ray reading; BMD of lumbar spine (L2-4), femoral neck (FN) and total hip:dual energy X-ray absorptiometry (DXA); Serum bone turnover markers and25(OH)D: automated Roche electrochemiluminescence system; Genotyping:TaqMan pre-designed SNP genotyping assays in real-time PCR System. Linear regression and binary logistic regression were used to test the associations of SNP genotypes, haplotypes and serum25(OH)D level, BMD, bone turnover markers, and low bone mass, fracture, and vertebral fracture.Results:1. In our sample1338women have vitamin D deficiency and another146women have vitamin D insufficiency, occupying89.6%and9.8%of total sample, respectively.2. The variants of rs222020(P=0.003) and rs2298849(P=3.73e-4) at GC are significantly associated with serum25(OH)D level. This association is still significant after10000times max(T) permutation test. Allele C of rs222020and allele G of rs2298849might be protective for serum25(OH)D level. Among the haplotypes of rs222020-rs2298849, CG (β=0.138,P=0.001) and TA (β=-0.118,P=0.002) correspond to increasing and decreasing serum25(OH)D concentrations, respectively. We didn’t find significant association between CYP2R1polymorphisms and serum25(OH)D level.3. No significant association were found between GC polymorphisms and BMD of L2-4, FN, and total hip, β-CTX, P1NP, and the risk of having abnormal BMD, fracture, or vertebral fracture. CYP2R1polymorphisms had similar results except its significant association with p-CTX and P1NP.Conclusion:GC variants have significant association with serum25(OH)D level among postmenopausal women of Han ethnic group in Beijing while CYP2R1variants weren’t found significant. Association of CYP2R1genetic variants with β-CTX and P1NP needs to be proven.更多还原