白癜风患者中 MTHFR、CBS 和 MTRR 多态性的高发率。一项回顾性研究的初步报告。

High incidence of MTHFR, CBS, and MTRR polymorphisms in vitiligo patients. Preliminary report in a retrospective study.

机构信息

Pathological Anatomy, Pineta Grande Hospital, Castel Volturno, Caserta, Italy.

出版信息

Eur Rev Med Pharmacol Sci. 2019 Jan;23(2):471-478. doi: 10.26355/eurrev_201901_16858.

DOI:10.26355/eurrev_201901_16858

PMID:30720153

Abstract

OBJECTIVE

Vitiligo is a multifactorial polygenic disorder with a complex pathogenesis. It is related to both genetic and no genetic factors. The role of genetics is currently studied with several analytical approaches, such as genetic linkage, candidate gene association studies, genome-wide association studies (GWAS), deep DNA re-sequencing and gene expression studies. To date, there are no genetic traits directly related to vitiligo pathogenesis.

PATIENTS AND METHODS

43 cases of vitiligo patients and 30 healthy donors recruited as control, were screened by assaying the biochemical molecules involved in the self-cells cytotoxicity (haptoglobin and homocysteine) and candidate genes involved in the regulatory process of the re-methylation cycles and transsulfuration. Candidate genes and their polymorphisms screened are methylene-tetrahydrofolate-reductase (MTHFR) C677T and A1298C; cystathionine-beta-synthase enzyme (CBS) I278T and Ins68bp; and methionine-synthase-reductase (MTRR) A66G.

RESULTS

A peculiar genetic profile in vitiligo patients are defined: 11.6% of vitiligo patients shown polymorphic variant MTHFR 677TT vs. 3.3% of healthy donor MTHFR 677CC profile (p=0.0017); 14.0% of vitiligo patients shown CBS polymorphic variant 278TT vs. 3.3% of healthy donor 278II profile (p=0.0012); and 11.6% of vitiligo patients shown MTRR 66GG vs. 3.3% of healthy donor MTRR 677AA profile (p>0.0001).

CONCLUSIONS

This is the first study reporting the correlation between the polymorphic status of MTHFR C677T, CBS I278T, and MTRR A66G and vitiligo. The genetic screening of these polymorphisms could be useful for early detection of the inheritance risk factor in a subject carrying relatives with vitiligo. Although these data could suggest a kind of dysregulation, genetically based, of thiols production mechanisms. Based on these results, we have not been able to get hypothesis about the putative pathogenesis of vitiligo, and the precise cause remains unclear.

摘要

目的

白癜风是一种具有复杂发病机制的多因素多基因疾病。它与遗传和非遗传因素有关。目前，遗传学的作用是通过几种分析方法来研究的，如遗传连锁、候选基因关联研究、全基因组关联研究（GWAS）、深度 DNA 重测序和基因表达研究。迄今为止，还没有与白癜风发病机制直接相关的遗传特征。

患者和方法

筛选了 43 例白癜风患者和 30 名健康对照者，检测了参与自身细胞细胞毒性的生化分子（结合珠蛋白和同型半胱氨酸）和参与再甲基化循环和转硫途径调节过程的候选基因。筛选的候选基因及其多态性为亚甲基四氢叶酸还原酶（MTHFR）C677T 和 A1298C；胱硫醚-β-合酶（CBS）I278T 和 Ins68bp；以及蛋氨酸合成酶还原酶（MTRR）A66G。

结果

定义了白癜风患者的特殊遗传特征：11.6%的白癜风患者显示 MTHFR 677TT 多态性变体，而 3.3%的健康供体 MTHFR 677CC 多态性（p=0.0017）；14.0%的白癜风患者显示 CBS 多态性变体 278TT，而 3.3%的健康供体 278II 多态性（p=0.0012）；和 11.6%的白癜风患者显示 MTRR 66GG，而 3.3%的健康供体 MTRR 677AA 多态性（p>0.0001）。