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摘要:
目的 了解四川凉山彝族成人脂肪和肥胖相关基因(fat mass and obesity associated gene,FTO)多态性与肥胖的关联。 方法 采用病例对照研究方法,病例组为彝族移民流行病学调查中收集的肥胖者[体重指数(body mass index,BMI)≥28 kg/m2],共322例;对照组为非肥胖非超重者(BMI < 24 kg/m2),按年龄和性别与病例组进行1:2频数匹配,共644例。采用TaqMan实时荧光定量聚合酶链式反应(polymerase chain reaction,PCR)法对FTO基因(rs1121980和rs17817449)进行基因分型。采用非条件Logistic回归分析模型分析两位点多态性与肥胖的关联。 结果 彝族农民中,加性模型和显性模型下,rs1121980位点与肥胖均存在统计学关联(加性模型:OR=1.45,95% CI:1.01~2.07,P=0.042;显性模型:OR=1.52,95% CI:1.01~2.31,P=0.048)。彝族农民中未见rs17817449与肥胖存在统计学关联(均有P>0.05)。彝族移民中,两位点(rs1121980和rs17817449)与肥胖均未见统计学关联(均有P>0.05)。 结论 彝族农民FTO rs1121980多态性与成人肥胖存在统计学关联,A等位基因是肥胖的危险因素。彝族移民FTO两位点与成人肥胖均未见关联。 Abstract:Objective To investigate the association between fat mass and obesity associated (FTO) gene and obesity in Yi adults in Sichuan Province. Methods A case-control study was performed by recruiting 322 obesity cases [body mass index (BMI)>28 kg/m2] from the Yi migrant study conducted in Sichuan Province. 644 non-overweight and non-obese controls were selected as control group (BMI < 24 kg/m2), they were frequency-matched to the cases by age and gender. FTO gene (rs1121980 and rs17817449) were genotyped using the TaqMan method.Unconditional Logistic regression analysis was used to test the association between genetic polymorphisms and obesity. Results The rs1121980 polymorphism was associated with obesity in Yi farmers (OR=1.45, 95% CI: 1.01-2.07, P=0.042, under additive model; OR=1.52, 95% CI: 1.01-2.31, P=0.048, under dominant model). No significant association between rs17817449 polymorphisms and obesity was observed in Yi farmers(all P>0.05). In Yi migrants, we found no significant association between the FTO single nucleotide polymorphism(SNP) and obesity(all P>0.05). Conclusion In Yi farmers, FTO rs1121980 polymorphism was independently associated with adult obesity. In Yi migrants, we found no significant association between the FTO SNPs and adult obesity. -
Key words:
- Yi people /
- FTO gene /
- Obesity /
- BMI /
- Migrant epidemiology
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表 1 不同移居状态病例组和对照组的基本特征比较[n(%)]
Table 1. The characteristics of cases and controls by migration status[n(%)]
变量 病例组(n=322) 对照组(n=643) 彝族人群 农民 移民 彝族人群 农民(n =126) 移民(n=196) 彝族人群 农民(n=462) 移民(n=181) χ2值 P值 χ2值 P值 χ2值 P值 性别 0.001 0.987 0.823 0.364 1.850 0.174 男性 107(33.23) 39(30.95) 68(34.69) 214(33.28) 163(35.28) 51(28.18) 女性 215(66.77) 87(69.05) 128(65.31) 429(66.72) 299(64.72) 130(71.82) 年龄(岁) 0.002 1.000 8.462 0.076 0.279 0.991 20~ 20(6.21) 12(9.52) 8(4.08) 40(6.22) 31(6.71) 9(4.98) 30~ 69(21.43) 32(25.40) 37(18.88) 137(21.31) 101(21.86) 36(19.89) 40~ 109(33.85) 51(40.48) 58(29.59) 218(33.90) 166(35.93) 52(28.73) 50~ 75(23.29) 25(19.84) 50(25.51) 150(23.33) 104(22.51) 46(25.41) ≥60 49(15.22) 6(4.76) 43(21.94) 98(15.24) 60(12.99) 38(20.99) 教育程度a 38.485 < 0.001 3.863 0.049 4.575 0.032 小学及以下 214(66.67) 108(85.71) 106(54.36) 541(84.14) 423(91.56) 118(65.19) 初中及以上 107(33.33) 18(14.29) 89(45.64) 102(15.86) 39(8.44) 63(34.81) 吸烟情况 0.784 0.376 0.328 0.567 0.034 0.854 从不吸烟 221(68.63) 85(67.46) 136(69.39) 423(65.79) 299(64.72) 124(68.51) 吸烟 101(31.37) 41(32.54) 60(30.61) 220(34.21) 163(35.28) 57(31.49) 饮酒情况 2.916 0.088 0.006 0.941 4.291 0.038 从不饮酒 184(57.14) 79(62.70) 105(53.57) 404(62.83) 288(62.34) 116(64.09) 饮酒 138(42.86) 47(37.30) 91(46.43) 239(37.17) 174(37.66) 65(35.91) 体力活动 13.712 0.001 10.114 0.006 0.984 0.612 轻 62(19.25) 19(15.08) 43(21.94) 150(23.33) 105(22.73) 45(24.86) 中 234(72.67) 101(80.16) 133(67.86) 474(73.72) 352(76.19) 122(67.40) 重 26(8.08) 6(4.76) 20(10.20) 19(2.95) 5(1.08) 14(7.74) 注:a教育程度缺失1人。 表 2 病例组和对照组SNP位点基因型分布和等位基因频率及Hardy-Weinbeng平衡检验
Table 2. Genotype distributions and allele frequencies of FTO SNPs and the test for Hardy-Weinberg equilibrium
SNP A1, A2 基因型(A2A2/A2A1/A1A1) MAF (%) HWE-P值 病例组 对照组 P值 病例组 对照组 P值 彝族人群 rs1121980 G, A 13/107/202 21/186/436 0.286 20.65 17.73 0.121 0.978 rs17817449 T, G 12/95/215 18/168/457 0.357 18.48 15.86 0.147 0.865 彝族农民 rs1121980 G, A 6/44/76 11/130/321 0.095 22.22 16.45 0.033 0.879 rs17817449 T, G 6/38/82 10/117/335 0.129 19.84 14.83 0.054 0.998 彝族移民 rs1121980 G, A 7/63/126 10/56/115 0.655 19.64 21.00 0.645 0.663 rs17817449 T, G 6/57/133 8/51/122 0.780 17.60 18.51 0.746 0.675 注:A1:野生型等位基因;A2:突变型等位基因;MAF:低频等位基因频率。 表 3 彝族成人FTO基因多态性与肥胖的关联
Table 3. Association of FTO SNPs with obesity in Yi adults
遗传模型 病例组 对照组 模型1 模型2 OR(95% CI)值 P值 OR(95% CI)值 P值 rs1121980 彝族人群 显性(GG/AA+AG) 202/120 436/207 1.25 (0.95~1.66) 0.116 1.20 (0.89~1.62) 0.227 隐性(AG+GG/AA) 309/13 622/21 1.25 (0.62~2.53) 0.540 1.05 (0.49~2.24) 0.901 加性(GG/AG/AA) 202/107/13 436/186/21 1.21 (0.95~1.54) 0.121 1.15 (0.89~1.49) 0.282 彝族农民 显性(GG/AA+AG) 76/50 321/141 1.51 (1.00~2.28) 0.050 1.52 (1.01~2.31) 0.048 隐性(AG+GG/AA) 120/6 451/11 1.99 (0.71~5.59) 0.192 1.72 (0.59~4.97) 0.320 加性(GG/AG/AA) 76/44/6 321/130/11 1.47 (1.03~2.09) 0.034 1.45 (1.01~2.07) 0.042 彝族移民 显性(GG/AA+AG) 126/70 115/66 0.97 (0.64~1.48) 0.888 0.94 (0.61~1.45) 0.781 隐性(AG+GG/AA) 189/7 171/10 0.62 (0.23~1.67) 0.339 0.60 (0.22~1.66) 0.327 加性(GG/AG/AA) 126/63/7 115/56/10 0.92 (0.65~1.31) 0.643 0.90 (0.63~1.29) 0.556 rs17817449 彝族人群 显性(TT/GG+GT) 215/107 457/186 1.22 (0.92~1.63) 0.170 1.17 (0.86~1.59) 0.333 隐性(GT+TT/GG) 310/12 625/18 1.35 (0.64~2.84) 0.435 1.16 (0.52~2.59) 0.724 加性(TT/GT/GG) 215/95/12 457/168/18 1.20 (0.94~1.54) 0.151 1.14 (0.87~1.48) 0.343 彝族农民 显性(TT/GG+GT) 82/44 335/127 1.43 (0.94~2.19) 0.097 1.43 (0.93~2.20) 0.101 隐性(GT+TT/GG) 120/6 452/10 2.23 (0.78~6.38) 0.136 1.92 (0.65~5.67) 0.240 加性(TT/GT/GG) 82/38/6 335/117/10 1.43 (0.99~2.05) 0.055 1.40 (0.97~2.02) 0.073 彝族移民 显性(TT/GG+GT) 133/63 122/59 0.99 (0.64~1.53) 0.963 0.96 (0.62~1.50) 0.858 隐性(GT+TT/GG) 190/6 173/8 0.68 (0.23~2.02) 0.486 0.64 (0.21~1.95) 0.436 加性(TT/GT/GG) 133/57/6 122/51/8 0.95 (0.66~1.37) 0.780 0.92 (0.63~1.35) 0.674 注:模型1:校正年龄,性别;模型2:校正年龄、性别、吸烟情况、饮酒情况、体力活动和教育程度。 表 4 彝族农民和移民FTO rs1121980多态性与BMI的关联(加性模型)
Table 4. Association of FTO rs1121980with BMI in Yi farmers and migrants considering the additive model
人群 [n(x±s)] 模型1 模型2 GG AG AA β(95% CI)值 P值 β(95% CI)值 P值 彝族农民 397 (22.33 ± 4.25) 174 (23.02 ± 4.72) 17 (24.10 ± 6.21) 0.75(0.08~1.41) 0.028 0.71(0.06~1.37) 0.033 彝族移民 241 (26.10 ± 5.10) 119 (25.93 ± 4.91) 17 (25.55 ± 4.13) -0.17(-1.05~0.72) 0.713 -0.18(-1.07~0.71) 0.690 注:模型1:校正年龄、性别;模型2:校正年龄、性别、吸烟情况、饮酒情况、体力活动和教育程度。 -
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