【摘要】 目的研究原发性甲状旁腺功能亢进症患者中钙敏感受体(CASR)基因多态性的分布,及其与临床特征的相关性。方法分别采用突变分离PCR(MS-PCR)和错配PCR-RFLP方法检测北京地区202名无亲缘关系的汉族健康妇女及45例原发性甲状旁腺功能亢进症(PHPT)患者CASR基因A986S、G990R基因型,测定血钙、游离钙、磷、甲状旁腺素(PTH)水平。结果(1)北京地区年轻正常汉族妇女中存在CASR基因A986S、G990R多态性,A986S等位基因A和S的频率分别为0.975和0.025,G990R等位基因R和G的频率分别为0.468和0.532,符合Hardy-Weinberg平衡。(2)PHPT患者:①A986S等位基因A和S的频率分别为0.944和0.056,G990R等位基因R和G的频率分别为0.667和0.333[与健康妇女组比较G990R基因型分布和等位基因频率差异有统计学意义(P<0.01)]。②AA、AS基因型组的血钙分别为(3.03±0.50)、(2.84±0.12)mmol/L(P<0.05),血游离钙分别为(1.56±0.32)、(1.42±0.07)mmol/L (P<0.05),血磷分别为(0.71±0.18)、(0.69±0.07)mmol/L(P>0.05),血PTH升高倍数分别为(13.13±11.26)、(9.25±7.78)倍(P<0.05)。(3)PHPT患者GG+GR与RR基因型组的血钙分别为(3.00±0.46)、(3.04±0.52)mmol/L(P<0.05),血游离钙分别为(1.50±0.21)、(1.58±0.39)mmol/L(P<0.05),血磷分别为(0.7l±0.16)、(0.71±0.18)mmol/L(P>0.05),血PTH升高倍数分别为(11.84±10.63)、(13.89±11.51)倍(P>0.05)。结论PHPT患者中CASR基因G990R多态性的分布频率与健康人群不同,R等位基因频率较高;A986S、G990R多态性与血钙、游离钙水平相关,含S或G等位基因的个体血钙及游离钙水平较低;A986S多态性与血PTH水平相关,含S等位基因的基因型的PTH水平较低。更多还原

【Abstract】 Objective To investigate the distribution of calcium-sensing receptor (CASR) gene polymorphism in patients with primary hyperparathyroidism (PHPT) in Beijing area and to explore the relationship between CASR genotype and related clinical characteristics.Methods A total of 202 healthy young women aged (27±5)years and 45 PHPT patients (M:F=13:32) aged (43±16) years were recruited in Beijing area.Whole blood genome DNA was extracted by QIAGEN DNA extraction kit.A986S and G990R genotypes were determined by mutagenically seperated polymerase chain reaction (MS-PCR) and PCR-RFLP respectively.Serum calcium, ionized calcium (ICa),phosphorus,PTH were determined.Results (1)There were A986S and G990R polymorphisms in healthy young women of Han nationality in Beijing.The frequencies of genotypes or alleles were AA 0.950,AS 0.050 or A 0.975,S 0.025 respectively for A986S,and RR 0.213,GR 0.510,GG 0.277 or R 0.468,G 0.532 respectively for G990R.Hardy-Weinberg equilibrium was evident.(2) In PHPT patients,①the frequencies of genotypes or alleles were AA 0.889,AS 0.111 or A 0.944,S 0.056,respectively for A986S,RR 0.422,GR 0.489 GG 0.089 or R and 0.667,G 0.333,respectively for G990R.The G990R genotype distribution between PHPT patients and healthy women was significantly different (P<0.01),and the frequency of R allele in G990R genotype was higher in PHPT group (P<0.01).②In patients carrying AA and AS genotypes, serum Ca was (3.03±0.50) vs (2.84±0.12) mmol/L (P<0.05),ICa was (1.56±0.32) vs (1.42±0.07) mmoL/L (P<0.05),serum P was (0.71±0.18) vs (0.69±0.07) mmol/L (P<0.05),serum PTH was (13.13±11.26) vs (9.25±7.78) times of normal uplimit (P<0.05).(3) In PHPT patients carrying GG+GR and RR genotype,serum Ca was (3.00±0.46) vs (3.04±0.52) mmol/L (P<0.05),ICa was (1.50±0.21) vs (1.58±0.39)mmol/L (P<0.01),serum Pwas (0.71±0.16) vs (0.71±0.18) mmol/L (P>0.05),serum PTHwas(11.84±10.63) vs (13.89±11.51) times of normal uplimit (P>0.05).Conclusion The distribution of G990R CASR genotype in PHPT patients is different from healthy women,and R allele is higher in PHPT group.Among PHPT patients,A986S and G990R polymorphisms are associated with serum calcium and ICa levels.Patients with S or G allele have lower levels of serum calcium and ICa.A986S genotype is also associated with serum PTH level and patients with S allele have relatively lower level of PTH.更多还原