Owiredu William K B A, Appiah Michael, Obirikorang Christian, Adu Evans Asamoah, Boima Vincent, Amos-Abanyie Ernestine Kubi, Akyaw Priscilla Abena, Owiredu Eddie-Williams, Acheampong Emmanuel
Department of Molecular Medicine, School of Medicine and Dentistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
Department of Medicine and Therapeutics, School of Medicine and Dentistry, College of Health Sciences, University of Ghana, Accra, Ghana.
Clin Hypertens. 2020 Aug 1;26:15. doi: 10.1186/s40885-020-00148-w. eCollection 2020.
Chronic kidney disease (CKD) is a significant comorbidity among hypertensive patients. Polymorphisms in the non-muscle myosin heavy chain 9 gene (MYH9) have been demonstrated to be significantly associated with CKD, among African- and European-derived populations. We investigated the spectrum of MYH9-associated CKD among Ghanaian hypertensive patients.
The study constituted a total of 264 hypertensive patients. Hypertensive patients with glomerular filtration rate (eGFR) < 60 ml/min/1.73m (CKD-EPI formula) or clinically diagnosed were defined as case subjects ( = 132) while those with eGFR ≥60 ml/min/1.73m were classified as control subjects ( = 132). Demographic data were obtained with a questionnaire and anthropometric measurements were taken. Five (5) millilitres (ml) of venous blood was drawn from study subjects into gel and EDTA vacutainer tubes. Two (2) mL of EDTA anticoagulated blood was used for genomic DNA extraction while three (3) mL of blood was processed to obtain serum for biochemical measurements. Genotyping of MYH9 polymorphisms (rs3752462) was done employing Tetra primer Amplification Refractory Mutation System (T-ARMS) polymerase chain reaction (PCR). Spot urine samples were also collected for urinalysis. Hardy-Weinberg population was assessed. Logistic regression models were used to assess the associations between single nucleotide polymorphisms and CKD.
The cases and control participants differed in terms of age, sex, family history, and duration of CKD (-value < 0.001). The minor allele frequencies of rs3752462 SNP were 0.820 and 0.567 respectively among the control and case subjects. Patients with the heterozygote genotype of rs3752462 (CT) were more likely to develop CKD [aOR = 7.82 (3.81-16.04)] whereas those with homozygote recessive variant (TT) were protective [aOR = 0.12 (0.06-0.25)]. Single nucleotide polymorphism of rs3752462 (CT genotype) was associated with increased proteinuria, albuminuria, and reduced eGFR.
We have demonstrated that MYH9 polymorphisms exist among Ghanaian hypertensive patients and rs3752462 polymorphism of MYH9 is associated with CKD. This baseline indicates that further longitudinal and multi-institutional studies in larger cohorts in Ghana are warranted to evaluate MYH9 SNP as an independent predictor of CKD among hypertensive patients in Ghana.
慢性肾脏病（CKD）是高血压患者中一种重要的合并症。在非洲和欧洲裔人群中，非肌肉肌球蛋白重链9基因（MYH9）的多态性已被证明与CKD显著相关。我们调查了加纳高血压患者中与MYH9相关的CKD情况。
该研究共纳入264例高血压患者。肾小球滤过率（eGFR）<60 ml/min/1.73m²（CKD-EPI公式）或临床诊断为CKD的高血压患者被定义为病例组（n = 132），而eGFR≥60 ml/min/1.73m²的患者被分类为对照组（n = 132）。通过问卷调查获取人口统计学数据并进行人体测量。从研究对象中抽取5毫升静脉血，分别注入凝胶管和EDTA真空管。2毫升EDTA抗凝血液用于基因组DNA提取，3毫升血液用于处理以获取血清进行生化检测。采用四引物扩增阻滞突变系统（T-ARMS）聚合酶链反应（PCR）对MYH9多态性（rs3752462）进行基因分型。还收集随机尿样进行尿液分析。评估哈迪-温伯格平衡。使用逻辑回归模型评估单核苷酸多态性与CKD之间的关联。
病例组和对照组在年龄、性别、家族史和CKD病程方面存在差异（P值<0.001）。rs3752462 SNP的次要等位基因频率在对照组和病例组中分别为0.820和0.567。rs3752462杂合子基因型（CT）的患者更易发生CKD [调整后比值比（aOR）= 7.82（3.81 - 16.04）]，而纯合子隐性变异（TT）的患者具有保护作用 [aOR = 0.12（0.06 - 0.25）]。rs3752462的单核苷酸多态性（CT基因型）与蛋白尿、白蛋白尿增加及eGFR降低相关。
我们已证明加纳高血压患者中存在MYH9多态性，且MYH9的rs3752462多态性与CKD相关。这一基线表明，有必要在加纳更大队列中进行进一步的纵向和多机构研究，以评估MYH9单核苷酸多态性作为加纳高血压患者CKD独立预测指标的价值。
