Analysis of PTH and ER Gene Polymorphisms in Patients with Type 2 Diabetes Mellitus Complicated with Osteoporosis
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摘要:
目的 探讨2型糖尿病(type 2 diabetes mellitus,T2DM)合并骨质疏松(osteoporosis,OP)患者甲状旁腺素(parathyroid hormone,PTH)及雌激素受体(estrogen receptor,ER)基因多态性特点。 方法 选取2022年11月至2023年10月在昆明市第一人民医院内分泌科住院的来自昆明地区T2DM患者110例,根据骨密度结果将其分组为T2DM无OP组(n = 68,T≥-1.0)、T2DM伴OP组(n = 42,T≤-2.5),检测其PTH及ER基因型及等位基因频率,比较其与性别、身高、体重等临床指标间的差异。 结果 回归分析显示,T2DM合并OP与患者性别、体重相关(P < 0.05),而PTH基因、ER基因多态性则无相关性(P > 0.05)。 结论 性别和体重是T2DM患者骨质疏松发生的独立危险因素;PTH基因、ER基因多态性与昆明地区T2DM伴OP的遗传易感性无关。 Abstract:Objective To investigate the characteristics of parathyroid hormone (PTH) and estrogen receptor (ER) gene polymorphisms in patients with type 2 diabetes mellitus (T2DM) complicated with osteoporosis (OP). Methods 110 patients with T2DM from Kunming area were selected in the 1st People’ s Hospital of Kunming Endocrinology Department from November 2022 to October 2023, and were divided into T2DM without OP group(n = 68, T≥-1.0), T2DM with OP group(n = 42, T≤-2.5), according to the results of bone mineral density , the genotype and allele frequency of PTH and ER were detected, and the differences between them and gender, height, weight and other clinical indicators were compared. Results Regression analysis showed that T2DM with OP was related to gende and weight (P < 0.05), but not related to PTH gene, or ER gene polymorphism (P > 0.05). Conclusion Gender and weight are independent risk factors for osteoporosis in patients with type 2 diabetes mellitus; gene polymorphism of PTH and ER are not related to the genetic susceptibility of T2DM with OP in Kunming area. -
Key words:
- gene polymorphism /
- type 2 diabetes mellitus /
- osteoporosis
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表 1 DNA提取所需仪器及试剂
Table 1. Equipment and reagents for DNA extraction
仪器及试剂 厂家 低温高速离心机 湖南可成仪器设备有限公司 −80 ℃超低温冰箱 海尔 移液枪 Eppendorf 电子天平 上海佑科仪器仪表公司 Arium bagtank 50(超纯水仪) 宁波丹斯博顿环保科技 微量核酸蛋白定量仪 Life Real PCR仪 ABI 微型离心机 珠海黑马医学仪器有限公司 电泳槽 北京六一生物科技有限公司 凝胶成像仪 Bio-RAD DNA提取试剂盒 TIANGEN DNA聚合酶(2×Taq Master Mix) GENERAY 引物(FuniCutTMBstBI,FuniCutTMPVull) 翌圣 DNA Marker GENERAY 琼脂糖 BioFROXX 50X TAE GENERAY GRred核酸染料 GENERAY 表 2 PTH基因、ER基因扩增所需引物
Table 2. Rimers for amplification of PTH and ER genes
引物名称 上游引物 引物长度(bp) 下游引物 引物长度(bp) PTH (BSTBI) 5'-CATTCTGTGTA
CTATAGTTTTG-3'22 5'-GAGCTTTGAATT
AGCA-3'16 ER(PVuII) 5'-CTGCCACCCTA
TCTGTATCTTTTCC
TATTCTCC -3'33 5'-TCTTTCTCTGCC
ACCCTGGCGTCGA
TTATCTGA-3'33 表 3 一般资料比较[($\bar x \pm s$),M(P25,P75)]
Table 3. Comparison of general data [($\bar x \pm s$),M(P25,P75)]
指标/组别 T2DM无骨质疏松组(n = 68) T2DM合并骨质疏松组(n = 42) χ2/t/Z P 性别(男/女) 38/30 2/40 29.321 0.001# 年龄(岁) 65.03±9.61 67.12±6.89 −1.331 0.186 吸烟(是/否) 11/57 2/40 3.246 0.072 饮酒(是/否) 15/53 5/37 1.800 0.180 收缩压(mmHg) 128.16±16.09 128.64±19.17 −0.142 0.888 舒张压(mmHg) 80.07±12.22 79.57±10.97 0.218 0.828 身高(m) 1.65±0.08 1.57±0.05 5.420 0.001# 体重(kg) 65.74±9.17 57.14±7.65 5.080 0.001# 体重指数(kg/m2) 24.28±2.76 23.16±3.35 1.897 0.060 TC(mmol/L) 4.84±0.97 4.90±0.98 −0.314 0.754 TG(mmol/L) 1.57(1.06,2.10) 1.67(0.99,2.40) 0.433 0.665 HDLC(mmol/L) 1.26±0.39 1.26±0.32 0.026 0.898 LDLC(mmol/L) 2.96±0.92 3.04±0.93 −0.410 0.682 HBA1c(%) 8.82(7.53,10.79) 8.64(7.73,9.93) −0.191 0.849 OGTT-0h(mmol/L) 8.18±2.17 9.20±2.51 −0.037 0.970 OGTT-2h(mmol/L) 16.62±4.86 15.46±4.34 1.212 0.228 INS-0h(mIU/L) 18.70(8.36,48.64) 16.32(8.53,64.55) 0.425 0.670 INS-2h(mIU/L) 45.09(26.22,75.53) 53.64(34.74,77.64) 1.256 0.209 HOMR-IR 5.12(2.22,15.94) 4.97(1.60,18.99) 0.271 0.787 UA(µmol/L) 312.00(231.25,372.00) 274.50(220.50,330.75) −1.467 0.142 血钙(mmol/L) 2.34±0.11 2.32±0.12 0.804 0.424 25-羟基维生素D (ng/mL) 23.23±7.72 22.45±9.01 0.477 0.634 Hs-CRP(mg/L) 1.42(0.59,2.62) 1.47(0.60,3.93) 0.691 0.490 FIB(g/L) 2.82(2.58,3.28) 2.89(2.45,3.32) 0.206 0.837 #P < 0.05。 表 4 PTH基因型分布频率比较[n(%)]
Table 4. Comparison of PTH genotype distribution frequencies[n(%)]
组别/基因型 BB Bb bb 合计(n) T2DM无骨质疏松组 48(70.6) 20(29.4) 0(0.0) 68 T2DM伴骨质疏松组 28(66.7) 13(31.0) 1(2.3) 42 合计(n) 76 33 1 110 χ2 = 0.187,P = 0.665。 表 5 PTH等位基因分布频率比较
Table 5. Comparison of PTH allele distribution frequencies
组别/基因型 频数 B b T2DM无骨质疏松组 136 116 20 T2DM伴骨质疏松组 84 69 15 χ2 = 0.385,P = 0.535。 表 6 ER基因型分布频率比较[n(%)]
Table 6. Comparison of ER genotype distribution frequencies[n(%)]
组别/基因型 PP Pp pp 合计(n) T2DM无骨质疏松组 18(26.5) 16(23.5) 34(50.0) 68 T2DM伴骨质疏松组 7(16.7) 22(52.3) 13(31.0) 42 合计n 25 38 47 110 χ2 = 9.559,P = 0.008。 表 7 ER等位基因分布频率比较
Table 7. Comparison of ER allele distribution frequencies
组别/基因型 频数 P p T2DM无骨质疏松组 136 52 84 T2DM伴骨质疏松组 84 36 48 χ2 = 0.462 ,P = 0.492。 表 8 Logistic回归分析结果
Table 8. Logistic analysis results
因素 B P OR 95%CI PTH基因型 0.000 1.000 1.000 0.359~2.786 ER基因型 −0.318 0.328 0.728 0.385~1.375 性别 −2.412 0.007 0.090 0.015~0.519 身高 −4.903 0.340 0.007 0.000~17.401 体重 −0.092 0.008 0.912 0.852~0.976 参考类别说明:“PTH基因型”中的BB型,"ER基因型中的PP型, “糖尿病有无骨质疏松”以糖尿病无骨质疏松,“性别”以女性作为参考类别。 -
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