具有HFE p.C282Y纯合性的血色素沉着症先证者中6号染色体p臂单核苷酸多态性微单倍型与IgG3水平

Chromosome 6p SNP microhaplotypes and IgG3 levels in hemochromatosis probands with HFE p.C282Y homozygosity.

作者信息

Barton James C, Barton J Clayborn, Cruz Eugénia, Teles Maria José, Guimarães João T, Porto Graça

机构信息

Southern Iron Disorders Center, Birmingham, AL, USA; Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.

Southern Iron Disorders Center, Birmingham, AL, USA.

出版信息

Blood Cells Mol Dis. 2020 Nov;85:102461. doi: 10.1016/j.bcmd.2020.102461. Epub 2020 Jun 27.

DOI:10.1016/j.bcmd.2020.102461

Abstract

Subnormal IgG1 or IgG3 levels occurred in 30% of hemochromatosis probands with HFE p.C282Y homozygosity and were concordant in HLA-identical siblings. We sought to identify factors associated with IgG subclasses in Alabama probands with p.C282Y homozygosity evaluated for 500 kb microhaplotypes AAT and GGG defined by SNPs in chromosome 6p genes PGBD1, ZNF193, and ZNF165. In regressions on IgG subclasses, we used: age; sex; GGG (dichotomous); iron removed to achieve depletion; CD8+ T-lymphocytes; and other IgG subclasses. Among 49 probands, AAT and GGG occurred in 95.9% and 16.3%, respectively. Thirteen probands (26.5%) had subnormal IgG1; 11 probands (22.4%) had subnormal IgG3. Mean IgG3 was higher in probands with than without GGG (75 mg/dL [95% confidence interval 63, 89] vs. 58 mg/dL [49, 71], respectively; p = 0.0321). Regression on IgG3 revealed: GGG positivity (p = 0.0106); and IgG1 (p = 0.0015). In a replication cohort of 22 Portugal probands with p.C282Y homozygosity, mean IgG3 was higher in probands with than without GGG (46 ± 16 vs. 31 ± 12 mg/dL, respectively; p = 0.0410). We conclude that mean IgG3 levels are higher in hemochromatosis probands with p.C282Y homozygosity with chromosome 6p microhaplotype GGG than in probands homozygous for microhaplotype AAT.

摘要

30%的HFE p.C282Y纯合子血色素沉着症先证者出现IgG1或IgG3水平低于正常，且在HLA相同的兄弟姐妹中情况一致。我们试图确定在阿拉巴马州对由6号染色体p基因PGBD1、ZNF193和ZNF165中的单核苷酸多态性定义的500 kb微单倍型AAT和GGG进行评估的p.C282Y纯合子先证者中，与IgG亚类相关的因素。在对IgG亚类的回归分析中，我们使用了：年龄；性别；GGG（二分变量）；为达到铁耗竭而去除的铁量；CD8 + T淋巴细胞；以及其他IgG亚类。在49名先证者中，AAT和GGG的出现率分别为95.9%和16.3%。13名先证者（26.5%）的IgG1低于正常；11名先证者（22.4%）的IgG3低于正常。有GGG的先证者的平均IgG3高于没有GGG的先证者（分别为75 mg/dL [95%置信区间63, 89] 与58 mg/dL [49, 71]；p = 0.0321）。对IgG3的回归分析显示：GGG阳性（p = 0.0106）；以及IgG1（p = 0.0015）。在一个由22名葡萄牙p.C282Y纯合子先证者组成的复制队列中，有GGG的先证者的平均IgG3高于没有GGG的先证者（分别为46±16与31±12 mg/dL；p = 0.0410）。我们得出结论，与微单倍型AAT纯合的先证者相比，具有6号染色体p微单倍型GGG的p.C282Y纯合子血色素沉着症先证者的平均IgG3水平更高。