Influence of Lewis α1-3/4-L-Fucosyltransferase (FUT3) Gene Mutations on Enzyme Activity, Erythrocyte Phenotyping, and Circulating Tumor Marker Sialyl-Lewis a Levels*
Influence of Lewis α1-3/4-L-Fucosyltransferase (FUT3) Gene Mutations on Enzyme Activity, Erythrocyte Phenotyping, and Circulating Tumor Marker Sialyl-Lewis a Levels*
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Lewis α1-3/4-L-岩藻糖基转移酶 (FUT3) 基因突变对酶活性、红细胞表型和循环肿瘤标志物唾液酸-Lewis a 水平的影响*
DOI：
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发表时间：
1996
影响因子：
4.8
通讯作者：
H. Wolf
中科院分区：
文献类型：
--
作者：
T. Ørntoft;E. M. Vestergaard;E. Holmes;J. S. Jakobsen;N. Grunnet;M. Mortensen;Philip J. Johnson;P. Bross;N. Gregersen;K. Skorstengaard;U. Jensen;L. Bolund;H. Wolf
携带α1-4岩藻糖残基的岩藻糖基化糖蛋白对于细胞粘附和作为肿瘤标志物是重要的。刘易斯基因FUT 3编码唯一已知的α1-4-岩藻糖基转移酶（FucT），缺乏这种酶类型的个体在红细胞上为路易斯阴性。我们检查了丹麦的刘易斯基因的突变谱，发现了6种不同的突变。其中T59 G、T202 C、C314 T、G508 A和T1067 A是常见的，而C445 A仅在40个个体中的一个个体中检测到。等位基因特异性聚合酶链反应以及FUT 3等位基因的克隆显示，202和314突变共同位于同一等位基因上。用具有202/314突变的等位基因转染的COS 7细胞缺乏酶活性。建立了聚合酶链反应-切割测定法用于健康个体以及20名真正的路易斯阴性癌症患者和10名非真正的癌症患者的基因分型。后者具有Lewis阴性红细胞，但唾液α1-4FucT活性。真正的Lewis阴性个体在两个FUT 3等位基因上都有突变。在66名健康个体中，检测到基因剂量效应，因为FUT 3杂合子个体的唾液中α1-4FucT活性低于纯合子野生型个体。杂合子个体中较低的酶水平导致血清中循环唾液酸-Lewis a结构的显著（p < 0.04）较低水平。这具有临床影响，即肿瘤标志物测定中的临界水平应根据基因分型确定。在非真正的路易斯阴性癌症患者组中，其红细胞在疾病期间从路易斯阳性转化为路易斯阴性，FUT 3杂合性显著（p < 0.05）更常见。
Fucosylated glycoproteins carrying α1-4 fucose residues are of importance for cell adhesion and as tumor markers. The Lewis gene, FUT3, encodes the only known α1-4-fucosyltransferase (FucT), and individuals who are deficient in this enzyme type as Lewis-negative on erythrocytes. We examined the mutational spectrum of the Lewis gene in Denmark and found 6 different mutations. Five, T59G, T202C, C314T, G508A, and T1067A, were frequent, and one, C445A, was only detected in one out of 40 individuals. Allele-specific polymerase chain reaction as well as cloning of FUT3 alleles showed that the 202 and 314 mutations were co-located on the same allele. COS7 cells transfected with an allele having the 202/314 mutations lacked enzyme activity. Polymerase chain reaction-cleavage assays were established for the genotyping of healthy individuals as well as 20 genuine Lewis-negative cancer patients and 10 non-genuine. The latter have Lewis-negative erythrocytes but saliva α1-4FucT activity. The genuine Lewis-negative individuals had mutations on both FUT3alleles. In 66 healthy individuals, a gene dosage effect was detected as FUT3 heterozygous individuals had a lower α1-4FucT activity in saliva than did homozygous wild-type individuals. The lower enzyme level in heterozygous individuals resulted in a significantly (p < 0.04) lower level of circulating sialyl-Lewis a structure in serum. This has the clinical impact that cut-off levels in tumor marker assays should be defined on the basis of genotyping. In the group of non-genuine Lewis-negative cancer patients, whose erythrocytes convert from Lewis-positive to Lewis-negative during the disease, FUT3 heterozygosity was significantly (p < 0.05) more common.
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影响因子：
20.3
作者：
T. Orntoft;Eric H. Holmes;Philip J. Johnson;Sen-itiroh Hakomori;Henrik Clausen
通讯作者：
T. Orntoft;Eric H. Holmes;Philip J. Johnson;Sen-itiroh Hakomori;Henrik Clausen
DOI：
10.1016/s0021-9258(19)45389-1
发表时间：
1982-12
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
John L. MagnaniS;Bo Nilssong;Manfred BrockhausSV;David Zopfl;Zenon SteplewskiJI;Hilary Koprowskill;V. Ginsburg
通讯作者：
John L. MagnaniS;Bo Nilssong;Manfred BrockhausSV;David Zopfl;Zenon SteplewskiJI;Hilary Koprowskill;V. Ginsburg
DOI：
10.1073/pnas.82.4.1199
发表时间：
1985-02
影响因子：
11.1
作者：
H. Clausen;S. Levery;E. Nudelman;S. Tsuchiya;S. Hakomori
通讯作者：
H. Clausen;S. Levery;E. Nudelman;S. Tsuchiya;S. Hakomori
DOI：
--
发表时间：
1994-06
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
S. Natsuka;K. M. Gersten;K. Zenita;R. Kannagi;J. Lowe
通讯作者：
S. Natsuka;K. M. Gersten;K. Zenita;R. Kannagi;J. Lowe
DOI：
10.1016/s0021-9258(19)47396-1
发表时间：
1991-09
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
J. B. Lowe;J. Kukowska-Latallo;R. P. Nair;R D Larsen;Rory M. Marks;B. Macher;R. Kelly;L. Ernst-L.
通讯作者：
J. B. Lowe;J. Kukowska-Latallo;R. P. Nair;R D Larsen;Rory M. Marks;B. Macher;R. Kelly;L. Ernst-L.