维生素D受体基因BsmⅠ多态性与北方汉族成人慢性肾功能不全骨密度的相关性

THE ASSOCIATION OF VITAMIN D RECEPTOR GENE POLYMORPHISM WITH BONE MINERAL DENSITY OF THE CHRONIC RENAL FAILURE PATIENTS AMONG NORTH CHINESE

目的探讨维生素D受体(VDR)基因BsmⅠ位点多态性与北方汉族成人慢性肾功能不全骨密度的关系,探讨影响骨密度的遗传易感因素。方法选取河北联合大学附属医院连续收治的汉族成人(年龄≥18岁)慢性肾功能不全患者211例,并根据血肌酐(Scr)水平分为肾功能不全组(110例)和肾功能衰竭组(101例),采用聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)的方法检测VDR基因BsmⅠ多态性位点,对慢性肾功能不全的相关因素进行问卷调查,同时检测入院24h内血甲状旁腺激素水平、血钾、血钠、血氯、血钙、血磷、肝肾功能、甲状腺功能及腰椎L2-4、颈椎、Wards三角3部位骨密度。应用Pearson相关分析年龄及体质指数(BMI)与骨密度之间的关系,再用协方差分析在对年龄、BMI校正后各部位骨密度与VDR基因型之间的关系。结果肾功能不全组和肾功能衰竭组VDR基因BsmⅠ多态性分布无统计学意义(χ2=0.088,P=0.591);年龄、BMI与骨密度的Pearson相关分析发现,BMI与骨密度值呈正相关(P<0.01);年龄与3部位的骨密度呈负相关(P<0.01)。应用协方差分析在对BMI与年龄进行校正后,对3部位的骨密度值与VDR基因型相关性进行分析,发现腰椎的骨密度值与VDR不同基因型之间的差异有统计学意义(P<0.05),aa基因型具有相对较低骨密度(P<0.05)。结论 VDR基因BsmⅠ位点多态性与慢性肾功能不全患者骨密度存在关联,可能是影响骨密度的遗传易感因素。

Objective To investigate the association of Vitamin D receptor gene polymorphisrn with bone mineral density of the chronic renal failure patients of the North China. Methods A total of 211 patients with chronic renal failure coming from unrelated familes who lived in the North China for many years were selected. The subjects were divided into chronic renal failure group（n = 110） and uremia group（n = 101） by the level of serum ereatinine. Polymerase chain reaction （PCR） and restriction fragment length polymor- phism （RFLP） technique were used to type VDR Bsm I polymorphisms. Information on environmental- related risk factors was collected using a pre- tested standard questionnaire. Bone mineral density Was measured by Dual energy X- way absorptiometry. Concentration of serum intact parathyroid hormone was measured by radioimmunoassay. Results The genotype frequency distribution of Vitamin D receptor gene followed the Hardy- Weinberg equilibrium（x^2 = 1. 034,P = 0. 210）. According to X2 test, it was no signifi- cant difference between chronic renal failure group and uremia group（x^2 = 0. 088, P =0. 591）. Body mass index had significant positive correlation with bone mineral density（P〈0.01）, while age had significant negative correlation with bone mineral density（P〈0.01）. People with aa genotype had significant lower bone mineral density in lumbar spine （P〈〈0.05） after correcting the body mass index and age. Conclusion The experimental results show that there is possible correlation between polymorphisms of restriction sites in Vitamin D receptor gene Bsm I and bone mineral density of the chronic renal failure patients of the North China and it indicates that the restriction site polymorphisms of Bsm I gene may be used as a genetic mark- ers.