Obesity-related genetic variants, human pigmentation, and risk of melanoma.
Obesity-related genetic variants, human pigmentation, and risk of melanoma.
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DOI：
10.1007/s00439-013-1293-4
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发表时间：
2013-07
期刊：
影响因子：
5.3
通讯作者：
Han, Jiali
中科院分区：
文献类型：
--
作者：
Li, Xin;Liang, Liming;Zhang, Mingfeng;Song, Fengju;Nan, Hongmei;Wang, Li-E;Wei, Qingyi;Lee, Jeffrey E.;Amos, Christopher I.;Qureshi, Abrar A.;Han, Jiali
以前的生物学研究表明，在动物模型和人类中，肥胖和色素沉着之间存在遗传联系。我们的研究调查了肥胖相关单核苷酸多态性（SNP）与人类色素沉着和黑色素瘤风险之间的个体和联合关联。FTO，MAP 2K 5，NEGR 1，FLJ 35779，ETV 5，CADM 2和NUDT 3基因中的8个肥胖相关SNP与5，876名欧洲血统个体的头发颜色名义上显著相关。结合35个独立肥胖风险基因座的遗传评分与深色头发显著相关（每10个等位基因的β系数=0.12，P值=4 10−5）。然而，单一SNPs或遗传评分显示与晒黑能力无显着关联。我们进一步研究了FTO位点的SNP与色素沉着和黑色素瘤风险的关系。在使用1000个基因组数据集的插补R平方质量度量>0.8的FTO基因中的783个SNP中，10个和3个独立的SNP分别与头发颜色和晒黑能力显著相关。此外，在1,804例病例和1,026例对照中，5个独立的FTO SNP与黑色素瘤风险存在名义上的显著相关性。但没有一个与肥胖相关或与肥胖相关变异连锁不平衡。FTO基因座可能导致人类色素沉着和黑色素瘤风险的变化，这可能与其对肥胖的影响无关。
Previous biological studies showed evidence of a genetic link between obesity and pigmentation in both animal models and humans. Our study investigated the individual and joint associations between obesity-related single nucleotide polymorphisms (SNPs) and both human pigmentation and risk of melanoma. Eight obesity-related SNPs in the FTO, MAP2K5, NEGR1, FLJ35779, ETV5, CADM2, and NUDT3 genes were nominally significantly associated with hair color among 5,876 individuals of European ancestry. The genetic score combining 35 independent obesity-risk loci was significantly associated with darker hair color (beta-coefficient per ten alleles=0.12, P-value=4 10−5). However, single SNPs or genetic scores showed non-significant association with tanning ability. We further examined the SNPs at the FTO locus for their associations with pigmentation and risk of melanoma. Among the 783 SNPs in the FTO gene with imputation R-square quality metric >0.8 using the 1000 genome data set, ten and three independent SNPs were significantly associated with hair color and tanning ability respectively. Moreover, five independent FTO SNPs showed nominally significant association with risk of melanoma in 1,804 cases and 1,026 controls. But none of them was associated with obesity or in linkage disequilibrium with obesity-related variants. FTO locus may confer variation in human pigmentation and risk of melanoma, which may be independent of its effect on obesity.
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