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南非印度裔和高加索裔银屑病关节炎患者的MTHFR C677T rs1801133和TP53 Pro72Arg rs1042522基因变异

MTHFR C677T rs1801133 and TP53 Pro72Arg rs1042522 gene variants in South African Indian and Caucasian psoriatic arthritis patients.

作者信息

Naidoo Pragalathan, Maharaj Ajesh B, Ghazi Terisha, Chuturgoon Anil A

机构信息

University of KwaZulu-Natal, Howard College, College of Health Sciences, School of Laboratory Medicine and Medical Sciences, Department of Medical Biochemistry, Durban, South Africa.

Walter Sisulu University, Faculty of Health Sciences, Department of Internal Medicine and Therapeutics, Eastern Cape, South Africa.

出版信息

Genet Mol Biol. 2025 Jan 10;48(1):e20230325. doi: 10.1590/1678-4685-GMB-2023-0325. eCollection 2025.

Abstract

Methylenetetrahydrofolate reductase (MTHFR) gene is involved in homocysteine and folic acid metabolism. Tumour suppressor protein TP53 gene maintains cellular and genetic integrity. To date, no studies associated the MTHFR C677T rs1801133 and TP53 Pro72Arg rs1042522 with CRP levels and methotrexate (a folic acid antagonist) treatment outcomes in psoriatic arthritis (PsA) patients. The present study aimed to investigate whether the MTHFR rs1801133 and TP53 rs1042522 gene variants influences CRP levels and methotrexate treatment outcomes in South African Indian and Caucasian PsA patients. PsA patients (n=114) and healthy controls (n=100) were genotyped for the rs1801133 and rs1042522 using RFLP-PCR. (i) Results for rs1801133 genotyping: Caucasian patients had a higher frequency of the variant T-allele versus healthy Caucasian controls (40% versus 22%; OR=2.31, 95% CI=1.10-4.88, p=0.0379). Patients with the variant CT+TT genotypes had higher median CRP levels at baseline versus wildtype CC genotypes (11.70 (5.3-28.80) mg/mL versus 7.40 (5.00-15.05) mg/mL, p=0.0355). After 6 months of methotrexate treatment median CRP levels between genotypes reduced and remained similar. (ii) Results for rs1042522 genotyping: Indian patients had a higher frequency of the variant Arg-allele versus healthy Indian controls (42% versus 29%; OR=1.75, 95% CI=1.07-2.86, p=0.0275). In conclusion, patients with the MTHFR rs1801133 variant T-allele have elevated CRP levels, which can be ameliorated with methotrexate.

摘要

亚甲基四氢叶酸还原酶(MTHFR)基因参与同型半胱氨酸和叶酸代谢。肿瘤抑制蛋白TP53基因维持细胞和遗传完整性。迄今为止,尚无研究将MTHFR C677T rs1801133和TP53 Pro72Arg rs1042522与银屑病关节炎(PsA)患者的C反应蛋白(CRP)水平及甲氨蝶呤(一种叶酸拮抗剂)治疗效果相关联。本研究旨在调查MTHFR rs1801133和TP53 rs1042522基因变异是否会影响南非印度裔和高加索裔PsA患者的CRP水平及甲氨蝶呤治疗效果。采用限制性片段长度多态性聚合酶链反应(RFLP-PCR)对114例PsA患者和100例健康对照进行rs1801133和rs1042522基因分型。(i)rs1801133基因分型结果:与健康高加索对照相比,高加索患者变异T等位基因频率更高(40%对22%;比值比[OR]=2.31,95%置信区间[CI]=1.10 - 4.88,p = 0.0379)。变异CT + TT基因型患者基线时的CRP中位数水平高于野生型CC基因型患者(11.70(5.3 - 28.80)mg/mL对7.40(5.00 - 15.05)mg/mL,p = 0.0355)。甲氨蝶呤治疗6个月后,各基因型之间的CRP中位数水平降低且保持相似。(ii)rs1042522基因分型结果:与健康印度对照相比,印度患者变异Arg等位基因频率更高(42%对29%;OR = 1.75,95% CI = 1.07 - 2.86,p = 0.0275)。总之,携带MTHFR rs1801133变异T等位基因的患者CRP水平升高,甲氨蝶呤可使其改善。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c8c/11721215/4a531637f404/1415-4757-GMB-48-1-e20230325-gf1.jpg

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