Homozygous single nucleotide polymorphism of the complement C1QA gene is associated with decreased levels of Clq in patients with subacute cutaneous lupus erythematosus
Homozygous single nucleotide polymorphism of the complement C1QA gene is associated with decreased levels of Clq in patients with subacute cutaneous lupus erythematosus
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DOI：
10.1191/0961203303lu329oa
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发表时间：
2003-01-01
期刊：
影响因子：
2.6
通讯作者：
Sontheimer, RD
中科院分区：
文献类型：
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作者：
Racila, DM;Sontheimer, CJ;Sontheimer, RD
我们报告了非家族性光敏性狼疮特异性皮肤病亚急性皮肤红斑狼疮 (SCLE) 与 CIQA 基因中新的单核苷酸多态性 (SNP) 之间的关联。我们还描述了该 SNP 与较低血清 Clq 水平之间的关联。该SNP由腺嘌呤取代位于C1QA基因第二外显子的氨基酸残基Gly70（位置不包括22个氨基酸前导肽）的密码子中的第三个鸟嘌呤组成。我们将该SNP指定为ClqA-Gly70(GGA)（该位置的GenBank序列为ClqA-G1y70(GGG)）。对 19 名 SCLE 患者的调查显示，11 名患者 (58%) 的 ClqA-Gly70GGA SNP 为纯合子，7 名患者 (37%) 为杂合子，只有 1 名患者 (5%) 的 GenBank 序列为纯合子。相比之下，62 个正常对照中只有 13 个 (21%) 的 ClqA-Gly70GGA SNP 是纯合的，41 个 (66%) 对照是杂合的，8 个 (13%) 对照是 GenBank 序列纯合的。因此，ClqA-Gly70(GGA) SNP 与 SCLE 密切相关（通过耶茨校正的卡方分析，P 值 = 0.005）。该 SNP 传统上被归类为临床沉默，因为它不编码不同的氨基酸。然而，我们的研究表明，该 SNP 似乎与 Clq 表达的功能异常相关，因为它的存在与 SCLE 患者和正常对照中 Clq 抗原蛋白的血清水平呈负相关。这种表型变化与翻译沉默（同义）ClqA-Gly70GGA 遗传变异相关的机制目前尚不清楚。
We report an association between a non-familial form of photosensitive Lupus-specific skin disease, subacute cutaneous lupus erythematosus (SCLE), and a new single nucleotide polymorphism (SNP) in the CIQA gene. We also describe an association between this SNP and lower levels of serum Clq. This SNP consists of adenine replacing the third guanine in the codon for amino acid residue Gly70 (position excludes the 22 amino acid leading peptide) that is located in the second exon of the ClQA gene. We have designated this SNP ClqA-Gly70(GGA) (the GenBank sequence at this location is ClqA-G1y70(GGG)). A survey of 19 SCLE patients showed that 11 (58%) were homozygous for ClqA-Gly70GGA SNP, seven (37%) were heterozygous, and only one patient (5%) was homozygous for the GenBank sequence. In contrast, only 13 of 62 (21%) normal controls were homozygous for the ClqA-Gly70GGA SNP, 41 (66%) controls were heterozygous and eight (13%) controls were homozygous for the GenBank sequence. Thus, the ClqA-Gly70(GGA) SNP is strongly associated with SCLE (P-value = 0.005 by chi-square analysis with Yates correction). This SNP would traditionally be classified as clinically silent as it does not encode a different amino acid. However, our studies have suggested that this SNP appears to be associated with a functional abnormality of Clq expression since its presence correlates inversely with serum levels of Clq antigenic protein in both SCLE patients and normal controls. The mechanism by which this phenotypic change is associated with the translationally silent (synonymous) ClqA-Gly70GGA genetic variation is currently unknown.