The melatonin receptor 1A (MTNR1A) gene is associated with recurrent and idiopathic calcium nephrolithiasis
The melatonin receptor 1A (MTNR1A) gene is associated with recurrent and idiopathic calcium nephrolithiasis
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DOI：
10.1093/ndt/gfr216
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发表时间：
2012-01-01
影响因子：
6.1
通讯作者：
Strazzullo, Pasquale
中科院分区：
文献类型：
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作者：
Esposito, Teresa;Rendina, Domenico;Strazzullo, Pasquale
背景实验证据表明，褪黑激素通过特定的褪黑激素受体（MTNR）位于几个鸟类和哺乳动物物种，包括人类的肾脏调节一些肾小管功能。我们假设褪黑激素受体1A基因（MTNR 1A）的单核苷酸多态性（SNPs）可能影响钙肾结石的风险。我们对246例复发性钙结石患者（136例男性，110例女性;平均年龄40.2 ± 12.0岁;体重指数25.8 ± 4.5 kg/m2）和269例年龄和性别相似且无肾结石病史的健康对照者的MTNR 1A基因进行了系统分析。MTNR 1A基因内含子1的两个SNPs：rs 13140012（P = 0.0004）和rs6553010（P = 0.009）与钙性肾结石显著相关。由两个SNPs产生的单倍型在结石形成者和对照之间的分布也不同，单倍型A-T在结石形成者中更常见（P = 0.00001），单倍型T-C在健康对照中更常见（P = 0.00001）。初步功能研究表明，SNP rs 13140012可以修饰转录因子的结合位点。该病例对照研究的结果表明MTNR 1A等位基因变异体与复发性钙性肾结石之间存在强相关性。
Background. Experimental evidence indicate that melatonin regulates some renal tubular functions via specific melatonin receptors (MTNRs) located in the kidney of several avian and mammalian species, including humans. We hypothesized that single nucleotide polymorphisms (SNPs) in the melatonin receptor 1A gene (MTNR1A) might influence the risk of calcium nephrolithiasis.Methods. We performed a systematic analysis of the MTNR1A gene in 246 recurrent calcium stone formers (136 men, 110 women; mean age 40.2 +/- 12.0 years; body mass index 25.8 +/- 4.5 kg/m(2)) and 269 healthy controls comparable for age and gender without a history of nephrolithiasis.Results. Two SNPs in Intron 1 of MTNR1A were significantly associated with calcium nephrolithiasis: rs13140012 (P = 0.0004) and rs6553010 (P = 0.009). The haplotypes resulting from the two SNPs were also differently distributed between stone formers and controls, the haplotype A-T being more represented among stone formers (P = 0.00001) and the haplotype T-C being more common in healthy controls (P = 0.00001). Preliminary functional studies showed that the SNP rs13140012 could modify the binding sites for transcription factors.Conclusion. The results of this case-control study indicate a strong association between allelic variants of MTNR1A and recurrent calcium nephrolithiasis.