一项基于临床的横断面研究，探索牙买加镰状细胞贫血中转甲基化和反硫化途径酶基因编码变异是否与个体间表型变异相关

IF 0.2 4区医学 Q4 MEDICINE, GENERAL & INTERNAL

West Indian Medical Journal Pub Date : 2017-10-26 DOI:10.7727/WIMJ.2017.205

S. Howell, K. Marshall, M. Reid, N. McFarlane‐Anderson, C. McKenzie

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引用次数: 1

摘要

目的:探讨镰状细胞贫血[纯合血红蛋白SS] (HbSS)中涉及转甲基化(亚甲基四氢叶酸还原酶(MTHFR)， 5-甲基四氢叶酸-同型半胱氨酸甲基转移酶(MTR))或反硫酸化(胱硫氨酸β -合成酶(CBS))代谢途径和临床相关表型测量的三个基因中四个双等位基因变异之间的潜在关联。方法:从牙买加莫纳西印度群岛大学镰状细胞科的镰状细胞诊所共招募了371名HbSS患者。采用基于聚合酶链反应的方法测定3个基因中的4个位点(MTHFR C677T、MTHFR A1298C、MTR A2756G和CBS 844ins68)的基因型。结果:单因素回归分析显示，MTHFR C677T与红细胞计数(p = 0.019)、MTHFR C677T与平均红细胞体积(p = 0.015)有统计学意义。多变量回归分析显示，MTHFR C677T与堆积细胞体积值(p = 0.019)、MTHFR C677T与RBC计数(p = 0.013)、MTHFR A1298C与红细胞平均血红蛋白浓度(p = 0.026)之间存在统计学显著相关性。结论:这项探索性横断面研究已经产生了新的和信息丰富的基因型-表型关联估计，但需要更大规模的研究来确定这些基因内的转甲基化和反硫化途径的特定变异是否与HbSS的个体间表型变异性有关。

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A Cross-sectional Clinic-based Study Exploring whether Variants within Genes Coding for Enzymes of the Transmethylation and Trans-sulphuration Pathways Are Associated with Inter-individual Phenotypic Variation in Sickle Cell Anaemia in Jamaica

Objective: To explore potential associations between four biallelic variants within three genes that code for enzymes involved in either the transmethylation (methylene tetrahydrofolate reductase (MTHFR), 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR)) or trans-sulphuration (cystathionine beta-synthase (CBS)) metabolic pathways, and clinically relevant phenotypic measures in sickle cell anaemia [homozygous haemoglobin SS] (HbSS). Methods: A total of 371 participants with HbSS disease were recruited from the Sickle Cell Clinic of the Sickle Cell Unit at The University of the West Indies, Mona, Jamaica. Genotypes at four sites (MTHFR C677T, MTHFR A1298C, MTR A2756G and CBS 844ins68) within the three genes were determined using polymerase chain reaction-based assays. Results: Univariate regression analyses showed statistically significant associations between MTHFR C677T and red blood cell (RBC) count (p = 0.019) and between MTHFR C677T and mean corpuscular volume (p = 0.015). Multivariable regression analyses showed statistically significant associations between MTHFR C677T and packed cell volume values (p = 0.019), between MTHFR C677T and RBC count (p = 0.013), and between MTHFR A1298C and mean corpuscular haemoglobin concentration (p = 0.026). Conclusion: This exploratory cross-sectional study has generated novel and informative genotype-phenotype estimates of association, but larger studies are needed to determine whether the specific variants within these genes underlying the transmethylation and trans-sulphuration pathways are related to inter-individual phenotypic variability in HbSS.

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来源期刊

West Indian Medical Journal 医学-医学：内科

CiteScore

0.20

自引率

0.00%

发文量

审稿时长

4-8 weeks

期刊介绍： The Journal is international in scope, with author and editorial contributions from across the globe. The focus is on clinical and epidemiological aspects of tropical and infectious diseases, new and re-emerging infections, chronic non-communicable diseases, and medical conditions prevalent in the Latin America-Caribbean region, and of significance to global health, especially in developing countries. The Journal covers all medical disciplines, as well as basic and translational research elucidating the pathophysiologic basis of diseases or focussing on new therapeutic approaches, and publishes original scientific research, reviews, case reports, brief communications, letters, commentaries and medical images. The Journal publishes four to six issues and four supplements annually. English is the language of publication but Abstracts are also duplicated in Spanish. Most of the articles are submitted at the authors’ initiative, but some are solicited by the Editor-in-Chief. Unless expressly stated, the Editorial Board does not accept responsibility for authors’ opinions. All papers on submission are reviewed by a subcommittee. Those deemed worthy for review are sent to two or three reviewers (one of the three might be a statistician if necessary). The returned papers with reviewer comments are reviewed by the Editor-in-Chief. Papers may be rejected, accepted or sent back to authors for revision. Resubmitted papers from authors are reviewed by the Editor-in-Chief and may be sent back to reviewers or a final decision made by Editor-in-Chief. The decision of the Editorial Board is final with regards to rejected articles. Rejected articles will not be returned to the authors. The editorial subcommittee has the right to return sub-standard manuscripts to the authors, rather than passing them on to the reviewers. This implies outright rejection of the manuscript.