Sequence variants in the 5′ flanking region of the leptin gene are associated with obesity in women
Sequence variants in the 5′ flanking region of the leptin gene are associated with obesity in women
复制标题
DOI：
10.1046/j.1469-1809.1999.6330227.x
复制
发表时间：
1999-05-01
影响因子：
1.9
通讯作者：
Price, RA
中科院分区：
文献类型：
--
作者：
Li, WD;Reed, DR;Price, RA
人类瘦素基因很少发现突变，并且瘦素基因序列变异与人类超重之间的关系尚不确定。为了确定瘦素基因及其调控元件的序列变异是否与极端肥胖有关，我们在125名不相关的极度肥胖（BMI大于等于40 kg/m(2)）和86名平均体重女性（BMI < 27 kg/m(2)）中筛选了类似3 kb的5'侧区和3个外显子。在蛋白质编码区只发现一个杂合沉默突变（密码子102；AAC/AAT）。在5'侧翼区，检测到6个频繁序列变异（q > 0.10），其中3个变异的等位基因频率在肥胖和平均体重的高加索女性之间存在差异(+19,chi(2) = 4.46, p = 0.035；-1823, chi(2) = 4.36, p = 0.037；-2548, chi(2) = 5.73, p = 0.017)。检测到9个不常见的序列变异（p < 0.05），但与平均体重的女性相比，肥胖女性的变异发生率并不高。对于极度肥胖的女性，三个多态性（+19，-188和-833）预测了肥胖程度。等位基因变异可能影响瘦素基因的调节，从而影响体重，尤其是在极度肥胖的女性中。然而，考虑到编码区域的低变异性和5'侧翼区域的高变异性，识别每个变体的功能意义可能是困难的。
Few mutations hare been found in the human leptin gene and the relationship between leptin gene sequence variation and human overweight is uncertain, To determine whether sequence variation within the leptin gene and its regulatory elements contribute to extreme obesity, we screened similar to 3 kb of the 5' flanking region and the three exons in 125 unrelated extremely obese (BMI greater than or equal to 40 kg/m(2)) and 86 average weight women (BMI < 27 kg/m(2)), Within the protein coding regions only one heterozygous silent mutation was found (codon 102; AAC/AAT). Within the 5' flanking region, six frequent sequence variants were detected (q > 0.10), and the allele frequencies of three of these variants differed between obese and average weight Caucasian women (+19, chi(2) = 4.46, p = 0.035; -1823, chi(2) = 4.36, p = 0.037; -2548, chi(2) = 5.73, p = 0.017). Nine infrequent sequence variants were detected (p < 0.05) but they did not occur more often among obese women compared with those of average-weight. For extremely obese women, three polymorphisms (+19, -188, and -833) predicted the degree of obesity. Allelic variants may influence the regulation of the leptin gene and thereby influence body weight, particularly among extremely obese women. However, given the low variability in coding regions and the high variability in the 5' flanking region, discerning the functional significance of each variant is likely to be difficult.