A+2138InsCAGACC polymorphism of the melanocortin receptor 3 gene is associated in human with fat level and partitioning in interaction with body corpulence
A+2138InsCAGACC polymorphism of the melanocortin receptor 3 gene is associated in human with fat level and partitioning in interaction with body corpulence
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DOI：
10.1007/bf03402008
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发表时间：
2002-03-01
影响因子：
5.7
通讯作者：
Chagnon, YC
中科院分区：
文献类型：
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作者：
Boucher, N;Lanouette, CM;Chagnon, YC
背景：黑素皮质素系统包括5种受体(MC1R到MC5R)，鼠和人的MC4R参与摄食的调节，鼠的MC3R参与体成分的调节。为了验证MC3R在人类中可能的相似作用，我们利用限制性片段长度多态(RFLP)和一个微卫星(D20S32e)分析了一个插入和一个单核苷酸多态性与身体成分和葡萄糖代谢的关系。方法：对812名魁北克家庭研究(QFS)队列的受试者进行了身体组成、食物摄入量和能量代谢表型的分析。用带有完整MC3R基因的Southern Blot检测到新的+2138InsCAGACC变异体。应用BsaJ1的聚合酶链式反应-限制性片段长度多态性分析方法，对G241a核苷酸突变引起的V8II氨基酸多态进行分型。应用聚合酶链式反应和全自动DNA测序仪对位于MC3R-1933/-1892之间的TG二核苷酸重复序列D20S32e进行分析。在基因型之间的协方差分析中，将年龄和性别作为协变量对表型进行了调整。食物摄入量和能量代谢表型也被调整为体重指数(BMI)，瘦素和腹部脂肪通过计算机断层扫描评估，使用6种皮褶厚度来评估肥胖。结果：+2138InsCAGACC MC3R基因多态与脂肪质量(FM)、体脂百分比(%Fate)和总腹部脂肪(ATF)存在关联。在正常体重(BMI和lt；25 kg/m(2))和超重(25：5 BMI和lt；30 kg/m(2))受试者中，+2138插入变异等位基因纯合子受试者表现出相似的肥胖水平，尽管BMI总体上存在差异。在正常体重中，插入等位基因纯合子的平均值高于杂合子和未插入的纯合子(%脂肪：24.0+/-1.1vs19.3+/-0.9和20.5+/-0.8，p=0.0005；调频：15.7+/-0.9 kg对11.7+/-0.7 kg和12.6+/-0.6 kg，p=0.0003)。相反，超重受试者变异等位基因纯合子的平均值较低(%脂肪：27.0+/-1.2vs31.4+/-0.8vs30.9+/-0.70，p=0.002；FM：18.3+/-1.0kgvs22.8+/-0.8kgvs22.80+/-10.6 kg，p=0.0001)。这导致两个BMI组插入等位基因纯合子与野生型等位基因携带者的体脂水平相似(%脂肪：+/-2-3%对+/-10-12%；FM：2公斤对+/-9-11公斤)。在肥胖受试者(体重指数大于或等于30 kg/m(2))中，ATF水平较低(-15%，p=0.002)。结论：一个新的+2138InsCAGACC MC3R多态与肥胖水平相关，并与体脂分配与肥胖存在交互作用。
Background: The melanocortin system includes five receptors (MC1R to MC5R), and mouse and human MC4R has been shown to be involved in the regulation of feeding, and mouse MC3R in body composition. To verify a possible similar effect of MC3R in humans, we analyzed one insertion and one single nucleotide polymorphism by restriction fragment length polymorphisms (RFLP), and a microsatellite (D20S32e) in relation to body composition and glucose metabolism.Methods: Eight hundred twelve subjects of the Quebec Family Study (QFS) cohort were analyzed for body composition, food intake, and energy metabolism phenotypes. Southern Blot with the complete MC3R cDNA was used to detect anew +2138InsCAGACC variant by PstI restriction. PCR-RFLP with BsaJ1 was used to type amino acid polymorphism V8II arising from a G241A nucleotide change. PCR and automatic DNA sequencers were used for the analysis of the TG dinucleotide repeat D20S32e located between -1933/-1892 of MC3R. In a covariance analysis among genotypes, phenotypes were adjusted for age and sex as covariates. Food intake and energy metabolism phenotypes were also adjusted for body mass index (BMI), and leptin and abdominal fat, as assessed by a computed tomography scan, for fatness using six skinfold thicknesses.Results: An association between the +2138InsCAGACC MC3R polymorphism was observed with fat mass (FM), percent body fat (%FAT), and total abdominal fat (ATF). Homozygote subjects for the +2138 insertion variant allele in normal weight (BMI < 25 kg/m(2)) and overweight (25 :5 BMI < 30 kg/m(2)) subjects showed a similar level of fatness despite the overall difference in BMI. In normal weight, homozygotes for the insertion allele showed higher mean values than heterozygotes and homozygotes for wild-type allele without insertion (%FAT: 24.0 +/- 1.1 versus 19.3 +/- 0.9 and 20.5 +/- 0.8, p = 0.0005; FM: 15.7 +/- 0.9 kg versus 11.7 +/- 0.7 kg and 12.6 +/- 0.6 kg, p = 0.0003). In contrast, overweight subjects homozygote for the variant allele showed lower mean values (%FAT: 27.0 +/- 1.2 versus 31.4 +/- 0.8 and 30.9 +/- 0.7, p = 0.002; FM: 18.3 +/- 1.0 kg versus 22.8 +/- 0.8 kg and 22.0 +/- 1 0.6 kg, p = 0.0001). This resulted in a similar level of body fat between both BMI groups for subjects homozygote for the insertion allele versus wild-type allele carriers (%FAT: +/-2-3% versus +/-10-12%; FM: 2 kg versus +/-9-11 kg). in obese subjects (BMI greater than or equal to 30 kg/m(2)), a lower level of ATF was seen (-15%, p = 0.002). Other polymorphisms and phenotypes tested showed no association.Conclusion: A new +2138InsCAGACC MC3R polymorphism is associated with the level of adiposity and with body fat partitioning in interaction with corpulence in humans.