酒精性股骨头坏死与亚甲基四氢叶酸还原酶677C／T单核苷酸多态性的关系

RELATIONSHIP BETWEEN ALCOHOL INDUCED OSTEONECROSIS OF FEMORAL HEAD AND SINGLE NUCLEOTIDE POLYMORPHISMS OF METHYLENE TETRAHYDROFOLATE REDUCTASE 677 C/T

目的研究亚甲基四氢叶酸还原酶(methylene tetrahydrofolate reductase,MTHFR)677C/T单核苷酸多态性与酒精性股骨头坏死(osteonecrosis of the femoral head,ONFH)的关系。方法选择2005年7月-2008年5月收治的89例酒精性ONFH男性患者作为试验组;年龄24～58岁,平均44.3岁。饮酒时间平均17年,平均每日饮白酒375mL。无其他与ONFH相关的疾病史,经影像学及病理检测证实为ONFH。选取健康男性自愿者77例作为对照组,年龄23～52岁,平均42.7岁。饮酒时间平均14年,平均每日饮白酒335mL。经影像学证实无ONFH。对每位受检者取血样2mL,提取DNA进行PCR扩增,对PCR产物进行DNA测序,根据所测DNA序列检测MTHFR677位点多态性,并对该位点C/T多态性进行统计学分析。结果对照组中MTHFR677 TT基因型频率及T等位基因频率分别为27.2%和52.0%(P>0.05),分布均符合Hardy-Weinberg平衡,结果有代表性。对照组MTHFR677基因型CC、CT、TT分布的例数(基因型频率)分别为18例(23.4%)、38例(49.4%)和21例(27.2%);试验组分别为13例(14.6%)、32例(36.0%)和44例(49.4%);两组比较差异有统计学意义(P<0.05)。对照组C、T等位基因分布的频数(频率)分别为74(48.0%)和80(52.0%),试验组分别为58(32.6%)和120(67.4%),两组比较差异有统计学意义(P<0.05)。C、T等位基因和TT基因型出现频率试验组高于对照组,两组比较差异有统计学意义(P<0.05);风险比值比分别为0.523、1.914和2.607,95%可信区间分别为0.335～0.816、1.226～2.987和1.359～5.001。CC及CT基因型出现频率两组间比较差异无统计学意义(P>0.05)。结论MTHFR677C/T多态性可能与酒精性ONFH的易感性相关。

Objective To explore the relationship between alcohol induced osteonecrosis of the femoral head （ONFH） and the single nucleotide polymorphisms （SNP） of methylene tetrahydrofolate reductase （MTHFR） 677 C/T. Methods From July 2005 to May 2008, eighty-nine male patients with alcohol induced ONFH were selected as the patient group, aged from 24 to 58 years old （mean 44.3 years old）. The time of drinking was about 17 years, 375 mL/day. The imaging evidence showed ONFH with no other history associated to ONFH. Seventy-seven male healthy adults were selected as the control group, aged from 23 to 52 years old （mean 42.7 years old）. The time of drinking was about 14 years, 335 mL/day. The imaging evidence showed no ONFH. The 2 mL blood sample was acquired from every subject. DNA was purified from leucocyte at first, then was amplicated by PCR, the product of PCR was sequenced at last. The SNP of MTHFR 677 C/T was analyzed with SPSS 12.0 software package. Results The TT genotype and T allele frequencies of MTHFR 677 C/T were 27.2% and 52.0% （P 〉 0.05） in the control group, and the distribution of genotype was consistent with Hardy-Weinberg equilibrium. The genotype frequencies of CC, CT and TT were 23.4% （18 cases）, 49.4% （38 cases） and 27.2% （21 cases） in the control group, were 14.6% （13 cases）, 36.0% （32 cases） and 49.4% （44 cases） in the patient group; showing statistically significant differences （P 〈 0.05）. The allele frequencies of C and T were 48.0% （74） and 52.0% （80） in the control group, and were 32.6% （58） and 67.4% （120） in the patient group; showing statistically significant differences （P 〈 0.05）. The frequencies of C, T alleles and TT genotype were higher in the patient group than in the control group, showing statistically significant differences （P 〈 0.05）. The odds ratios were 0.523, 1.914 and 2.607, respectively; the 95% confidence interval were 0.335-0.816, 1.226-2.987, 1.359-5.001, respectively. Conclusion The relationship may exist between the SNP of MTHFR 677 C/T and alcohol induced ONFH.