目的探究α-辅肌动蛋白3（ACTN3）基因多态性与绝经后女性肌肉强度的相关性。方法纳入北京市东城区34个社区598例绝经后女性，年龄（62．9±7．0）岁。通过Sequenom Mass Array平台对ACTN3基因rs540874、rs618838、rs2229456位点进行基因分型，并分析其与绝经后女性肌肉强度的相关性。其中163例给予强化运动训练，271例给予钙剂600mg／d＋普通维生素D800U／d或骨化三醇0．25μg／d，随访2年，观察强化运动及维生素D补充后肌力变化与ACTN3基因型的相关性。结果rs540874位点不同基因型组间站立试验时间差异有统计学意义[GG（9．02±3．85）s比GA（9．27±4．14）S比AA（9．68±5．00）s，P=0．015]。G等位基因携带者右手握力具有高于A等位基因携带者的趋势，但差异无统计学意义[GG（24．53±5．45）N比GA（24．26±4．79）N比AA（23．66±4．32）N，P=0．056]。多重线性回归显示，AA基因型的受试者站立试验较GA、GG基因型显著延长（B=2．639，95％C1：1．632-4．646，P=0．010）。rs618838、rs2229456基因型与双手握力及站立试验时间均无明显相关性（均P〉0．05）。此外，rs540874位点G等位基因携带者、rs618838位点c等位基因携带者、rs2229456位点A等位基因携带者强化运动及维生素D补充后下肢肌力均显著增加（均P〈0．05）。结论ACTN3基因的rs540874位点与绝经后女性下肢肌力相关；rs540874、rs618838、rs2229456位点不同基因型可能与干预后下肢肌力获益有关。
Background It is widely recognized that the diagnosis of parathyroid carcinoma （PC） is often difficult because of the overlap of characteristics between malignant and benign parathyroid tumors, especially at an early stage. Our study aimed to investigate the differential expression of Ki-67, galectin-3, fragile histidine triad （FHIT） gene, and parafibromin in PC, parathyroid adenoma （PA）, parathyroid hyperplasia （PH）, and normal parathyroid （NP） tissues; then to assess these expression values for use in differential diagnosis of malignant and benign parathyroid tumors. Methods Data of 15 cases with PC, 19 PAs, and 8 PHs were retrospectively analyzed for their clinical characteristics. The expression of Ki-67, galectin-3, FHIT, and parafibromin were detected via immunohistochemistry in the above-mentioned specimens and 6 NPs as control. Results Complete loss of parafibromin expression was seen in 9 of 15 （60%） carcinomas, and all normal parathyroid tissues and parathyroid benign tumors stained positive for parafibromin except for one （4%） adenoma. Galectin-3 staining was positive in 11 of 15 （73%） carcinomas, 5 of 19 （26%） adenomas, 1 of 8 （12%） hyperplasias, and 0 of 6 normal tissues. The Ki-67 proliferative index was high in 4 of 15 （27%） carcinomas, 1 of 19 （5%） adenomas, and none of the hyperplasia or normal tissues. FHIT expression did not differ appreciably among the tumor types. The combination of overexpression of galectin-3 or loss of parafibromin increased sensitivity for PC to 87%, while the specificity of both positive galectin-3 and positive Ki-67 could reach 100%. Conclusions These data suggested that loss of parafibromin and overexpression of galectin-3 and Ki-67 might help to distinguish parathyroid carcinoma from other parathyroid tumors. And the combination of two or three of these markers might produce better sensitivity and/or specificity for the diagnosis of parathyroid carcinoma.
