Hart Sailors M L, Folsom A R, Ballantyne C M, Hoelscher D M, Jackson A S, Linda Kao W H, Pankow J S, Bray M S
Department of Pediatrics, Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX 77030, USA.
Diabetes Obes Metab. 2007 Jul;9(4):548-57. doi: 10.1111/j.1463-1326.2006.00637.x.
To investigate the effects of variation in the leptin [LEP (19A>G)] and melanocortin-4 receptor [MC4R (V103I)] genes on obesity-related traits in 13 405 African-American (AA) and white participants from the Atherosclerosis Risk in Communities (ARIC) Study.
We tested the association between the single-locus and multilocus genotypes and obesity-related measures [body mass index (BMI), body weight (BW), waist-hip ratio, waist circumference and leptin levels], adjusted for age, physical activity level, smoking status, diabetic status, prevalence of coronary heart disease, hypertension, stroke or transient ischaemic attack.
AA and white female carriers of the MC4R I103 allele exhibited significantly lower BW than non-carriers of this allele (p < 0.05 and p < 0.01 respectively). AA female carriers of both the LEP A19 allele and the MC4R I103 allele were 63% [odds ratio (OR) = 0.37, 95% confidence interval (CI) (0.18-0.78)] less likely to be obese, and white female carriers of the same two alleles were 46% [OR = 0.54, 95% CI (0.32-0.91)] less likely to be obese, than non-carriers of the variant alleles. Female carriers of both the LEP A19 and MC4R I103 alleles had significantly lower BW (p < 0.05), BMI (p < 0.05) and plasma leptin (p < 0.01) than the non-carriers of both the alleles. Carriers of the two variant alleles had lower BMI over the 9-year course of the ARIC study and significantly lower weight gain from age 25 years. No significant joint effect of these two variants was observed in males.
These results suggest that variation within the LEP and MC4R genes is associated with reduced risk for obesity in females.
在社区动脉粥样硬化风险（ARIC）研究的13405名非裔美国人（AA）和白人参与者中，研究瘦素基因[LEP (19A>G)]和黑皮质素4受体基因[MC4R (V103I)]的变异对肥胖相关特征的影响。
我们测试了单基因座和多基因座基因型与肥胖相关指标[体重指数（BMI）、体重（BW）、腰臀比、腰围和瘦素水平]之间的关联，并对年龄、身体活动水平、吸烟状况、糖尿病状态、冠心病、高血压、中风或短暂性脑缺血发作的患病率进行了校正。
MC4R I103等位基因的AA和白人女性携带者的BW显著低于该等位基因的非携带者（分别为p < 0.05和p < 0.01）。与变异等位基因的非携带者相比，LEP A19等位基因和MC4R I103等位基因的AA女性携带者肥胖的可能性降低63%[比值比（OR）= 0.37，95%置信区间（CI）（0.18 - 0.78）]，相同两个等位基因的白人女性携带者肥胖的可能性降低46%[OR = 0.54，95% CI（0.32 - 0.91）]。LEP A19和MC4R I103等位基因的女性携带者的BW（p < 0.05）、BMI（p < 0.05）和血浆瘦素（p < 0.01）均显著低于两个等位基因的非携带者。在ARIC研究的9年过程中，两个变异等位基因的携带者BMI较低，且从25岁起体重增加显著较低。在男性中未观察到这两个变异的显著联合效应。
这些结果表明，LEP和MC4R基因内的变异与女性肥胖风险降低有关。
