Fat mass-and obesity-associated (FTO) gene variant is associated with obesity: longitudinal analyses in two cohort studies and functional test.
Fat mass-and obesity-associated (FTO) gene variant is associated with obesity: longitudinal analyses in two cohort studies and functional test.
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作者：
Qi L;Kang K;Zhang C;van Dam RM;Kraft P;Hunter D;Lee CH;Hu FB
目的：研究脂肪量和肥胖相关（FTO）变异体与肥胖、循环脂肪因子水平和人和小鼠各种材料中FTO表达的纵向关联。研究设计和方法-我们对来自两个前瞻性队列的2,287名男性和3,520名女性进行rs 9939609基因分型。在糖尿病男性（n = 854）和女性（n = 987）的一个子集中测量血浆脂联素和瘦素。在来自db/db小鼠和小鼠巨噬细胞的脂肪细胞中测试FTO的表达。我们观察到rs 9939609和BMI之间的相关性在男性老年（≥65岁）时呈下降趋势，而在女性的不同年龄组中，这种相关性是恒定的。此外，单核苷酸多态性（SNP）rs 9939609与血浆脂联素水平降低相关（TT、TA和AA基因型的log[e]−均值分别为1.82 ± 0.04、1.73 ± 0.03和1.68 ± 0.05;趋势P = 0.02）和瘦素（log[e]−均值，3.56 ± 0.04，3.63 ± 0.04和3.70 ± 0.06;趋势P = 0.06）。BMI的调整减弱了这种关联。FTO基因在人和小鼠组织中普遍表达，包括脂肪细胞。在db/db小鼠脂肪细胞的辅助研究中，FTO表达比野生型小鼠低约50%。结论：FTO SNP rs 9939609与肥胖风险之间的关联可能在老年时下降。该变体通过BMI的变化影响循环脂联素和瘦素水平。此外，FTO基因在db/db小鼠脂肪细胞中的表达降低。
OBJECTIVE—To examine the longitudinal association of fat mass–and obesity-associated (FTO) variant with obesity, circulating adipokine levels, and FTO expression in various materials from human and mouse. RESEARCH DESIGN AND METHODS—We genotyped rs9939609 in 2,287 men and 3,520 women from two prospective cohorts. Plasma adiponectin and leptin were measured in a subset of diabetic men (n = 854) and women (n = 987). Expression of FTO was tested in adipocytes from db/db mice and mouse macrophages. RESULTS—We observed a trend toward decreasing associations between rs9939609 and BMI at older age (≥65 years) in men, whereas the associations were constant across different age groups in women. In addition, the single nucleotide polymorphism (SNP) rs9939609 was associated with lower plasma adiponectin (log[e]− means, 1.82 ± 0.04, 1.73 ± 0.03, and 1.68 ± 0.05 for TT, TA, and AA genotypes, respectively; P for trend = 0.02) and leptin (log[e]− means, 3.56 ± 0.04, 3.63 ± 0.04, and 3.70 ± 0.06; P for trend = 0.06) in diabetic women. Adjustment for BMI attenuated the associations. FTO gene was universally expressed in human and mice tissues, including adipocytes. In an ancillary study of adipocytes from db/db mice, FTO expression was ∼50% lower than in those from wild-type mice. CONCLUSIONS—The association between FTO SNP rs9939609 and obesity risk may decline at older age. The variant affects circulating adiponectin and leptin levels through the changes in BMI. In addition, the expression of FTO gene was reduced in adipocytes from db/db mice.
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影响因子：
158.5
作者：
Hu, FB;Manson, JE;Willett, WC
通讯作者：
Willett, WC
影响因子：
8.7
作者：
Hotta, K;Funahashi, T;Matsuzawa, Y
通讯作者：
Matsuzawa, Y
DOI：
10.1126/science.1151710
发表时间：
2007-11-30
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gerken T;Girard CA;Tung YC;Webby CJ;Saudek V;Hewitson KS;Yeo GS;McDonough MA;Cunliffe S;McNeill LA;Galvanovskis J;Rorsman P;Robins P;Prieur X;Coll AP;Ma M;Jovanovic Z;Farooqi IS;Sedgwick B;Barroso I;Lindahl T;Ponting CP;Ashcroft FM;O'Rahilly S;Schofield CJ
通讯作者：
Schofield CJ
影响因子：
56.9
作者：
Frayling, Timothy M.;Timpson, Nicholas J.;McCarthy, Mark I.
通讯作者：
McCarthy, Mark I.
影响因子：
82.9
作者：
Berg, AH;Combs, TP;Scherer, PE
通讯作者：
Scherer, PE