Allele variations in the OCA2 gene (pink-eyed-dilution locus) are associated with genetic susceptibility to melanoma
Allele variations in the OCA2 gene (pink-eyed-dilution locus) are associated with genetic susceptibility to melanoma
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DOI：
10.1038/sj.ejhg.5201415
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发表时间：
2005-08-01
影响因子：
5.2
通讯作者：
Melan-Cohort
中科院分区：
文献类型：
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作者：
Jannot, AS;Meziani, R;Melan-Cohort
隐匿性白化病2 （OCA2）基因位于15q11，编码一种黑色素体跨膜蛋白，该蛋白与最常见的人类隐匿性皮肤白化病有关。隐匿性皮肤白化病是一种人类遗传疾病，其特征是色素沉着，易患皮肤癌。我们想知道这个位点的等位基因变异是否会影响对恶性黑色素瘤（MM）的易感性。总共对113名黑色素瘤患者和105名没有个人或家族皮肤癌病史的白种人对照进行了10个基因内单核苷酸多态性（snp）的基因分型。通过比较病例和对照组之间的等位基因分布，我们发现MM和OCA2是相关的（经多次检验校正后p值= 0.030）。然后，最近开发的一种策略，“组合测试”使我们能够证明由两个snp形成的组合与MM的相关性最强，这表明基因内snp之间可能存在相互作用。此外，考虑到黑色素皮质素1受体基因（MC1R，一个关键的色素沉着基因）的变异存在以及所有色素沉着特征作为黑色素瘤的危险因素，使用logistic模型也检测了OCA2对MM风险的作用。我们的数据表明，除了MC1R外，第二种色素沉着基因也与黑色素瘤的遗传易感性有关。
The occuloalbinism 2 ( OCA2) gene, localized at 15q11, encodes a melanosomal transmembrane protein that is involved in the most common form of human occulo-cutaneous albinism, a human genetic disorder characterized by fair pigmentation and susceptibility to skin cancer. We wondered whether allele variations at this locus could influence susceptibility to malignant melanoma ( MM). In all, 10 intragenic single-nucleotide polymorphisms ( SNPs) were genotyped in 113 patients with melanomas and in 105 Caucasian control subjects with no personal or family history of skin cancer. By comparing allelic distribution between cases and controls, we show that MM and OCA2 are associated ( p value = 0.030 after correction for multiple testing). Then, a recently developed strategy, the 'combination test' enabled us to show that a combination formed by two SNPs was most strongly associated to MM, suggesting a possible interaction between intragenic SNPs. In addition, the role of OCA2 on MM risk was also detected using a logistic model taking into account the presence of variants of the melanocortin 1 receptor gene ( MC1R, a key pigmentation gene) and all pigmentation characteristics as melanoma risk factors. Our data demonstrate that a second pigmentation gene, in addition to MC1R, is involved in genetic susceptibility to melanoma.