Ruggeri R M, Vicchio T M, Giovinazzo S, Certo R, Alibrandi A, Trimarchi F, Benvenga S, Trovato M
Department of Clinical and Experimental Medicine, Endocrine Unit, University of Messina, Padiglione H, 4 Piano, AOU Policlinico Universitario "G. Martino", via Consolare Valeria, 1, 98125, Messina, Italy.
Department of Statistical Sciences (SEFISAST), University of Messina, Messina, Italy.
J Endocrinol Invest. 2015 Nov;38(11):1175-82. doi: 10.1007/s40618-015-0292-9. Epub 2015 May 3.
p53, which is encoded by the tumor suppressor gene TP53, plays a crucial role in the regulation of mechanisms of cell cycle arrest and apoptosis. Some SNPs of TP53, involving a different apoptotic ability of p53, have been associated with increased susceptibility to develop autoimmune diseases as well as cancer. We investigated the genotypic distribution of TP53 exon 4 SNPs in a cohort of Caucasian patients affected by Hashimoto's thyroiditis (HT).
Peripheral blood for DNA extraction was collected from 109 Caucasian unrelated subjects, 79 HT patients and 30 healthy controls. SNPs analysis was carried out by amplification and sequencing of exon 4 TP53.
For the Pro72Arg (rs 1042522) SNP we found these rates in HT patients: 11.4% wild-type C/C (Pro72Pro), 24.0% heterozygous G/C (Pro72Arg), 64.6% homozygous G/G (Arg72Arg). The corresponding rates in healthy controls were 10, 46.7 and 43.3%, respectively. Thus, significantly different were G/C heterozygosity (24.0 vs 46.7 %, p = 0.039) and G/G homozygosity (64.6 vs 43.3%, p = 0.042). These differences were also confirmed when comparing our study population to published Caucasian control groups. The other described SNPs (Pro34Pro rs 11575998, Pro36Pro rs1800370, Pro47Ser rs1800371, and Arg110Leu rs 11540654) were absent or very rare in our study population.
Our preliminary data, the first on a Caucasian population, indicate an increased prevalence of the homozygous genotype Arg/Arg and a decreased prevalence of heterozygous genotype Arg/Pro of rs 1042522 in HT patients compared to controls, suggesting that such SNP may contribute to confer susceptibility to HT.
由肿瘤抑制基因TP53编码的p53在细胞周期停滞和凋亡机制的调控中起关键作用。TP53的一些单核苷酸多态性（SNP），涉及p53不同的凋亡能力，与自身免疫性疾病以及癌症的易感性增加有关。我们调查了一组患有桥本甲状腺炎（HT）的白种人患者中TP53第4外显子SNP的基因型分布。
从109名无亲缘关系的白种人、79名HT患者和30名健康对照者中采集用于DNA提取的外周血。通过对TP53第4外显子进行扩增和测序来进行SNP分析。
对于Pro72Arg（rs 1042522）SNP，我们在HT患者中发现以下比例：11.4%野生型C/C（Pro72Pro），24.0%杂合子G/C（Pro72Arg），64.6%纯合子G/G（Arg72Arg）。健康对照者中的相应比例分别为10%、46.7%和43.3%。因此，G/C杂合性（24.0%对46.7%，p = 0.039）和G/G纯合性（64.6%对43.3%，p = 0.042）存在显著差异。当将我们的研究人群与已发表的白种人对照组进行比较时，这些差异也得到了证实。其他所描述的SNP（Pro34Pro rs 11575998、Pro36Pro rs1800370、Pro47Ser rs1800371和Arg110Leu rs 11540654）在我们的研究人群中不存在或非常罕见。
我们的初步数据是关于白种人群体的首个数据，表明与对照组相比，HT患者中rs 1042522的纯合基因型Arg/Arg患病率增加，杂合基因型Arg/Pro患病率降低，提示这种SNP可能有助于赋予对HT的易感性。
