Yahya Mohd Jokha, Ismail Patimah Binti, Nordin Norshariza Binti, Akim Abdah Binti Md, Binti Md Yusuf Wan Shaariah, Adam Noor Lita Binti, Zulkifli Nurul Fasihah
Department of Biomedical, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Seri Kembangan, Malaysia.
Department of Human Development and Growth, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Seri Kembangan, Malaysia.
J Nutr Metab. 2019 Jan 3;2019:8736215. doi: 10.1155/2019/8736215. eCollection 2019.
Type 2 diabetes mellitus (T2DM) is associated with a high incidence of nephropathy. The aim of this study was to investigate the association of a genetic polymorphism of carnosinase ( and -), endothelial nitric oxide synthase (), and manganese superoxide dismutase () genes with the development of diabetic nephropathy among Malaysian type 2 diabetic patients. A case-control association study was performed using 652 T2DM patients comprising 227 Malays (without nephropathy = 96 and nephropathy = 131), 203 Chinese (without nephropathy = 95 and nephropathy = 108), and 222 Indians (without nephropathy = 136 and nephropathy = 86). DNA sequencing was performed for the of , while the rest were tested using DNA Sequenom MassARRAY to identify the polymorphisms. DNA was extracted from the secondary blood samples taken from the T2DM patients. The alleles and genotypes were tested using four genetic models, and the best mode of inheritance was chosen based on the least value. The of was significantly associated with diabetic nephropathy among the Indians only with OR = 1.94 and 95% CI = (1.76-3.20) and fitted best the multiplicative model, while was associated among all the three major races with the Malays having the strongest association with OR = 2.46 and 95% CI = (1.48-4.10), Chinese with OR = 2.26 and 95% CI = (1.34-3.83), and Indians with OR = 1.77 and 95% CI = (1.18-2.65) in the genotypic multiplicative model. The best mode of inheritance for both and was the additive model. For -, the Chinese had OR = 2.8 and 95% CI = (0.53-14.94), Indians had OR = 2.4 and 95% CI = (0.69-2.84), and Malays had OR = 2.16 and 95% CI = (0.54-8.65), while for -, the Indians had the highest risk with OR = 3.16 and 95% CI = (0.52-17.56), followed by the Chinese with OR = 3.55 and 95% CI = (0.36-35.03) and the Malays with OR = 2.89 and 95% CI = (0.29-28.32). The four oxidative stress-related polymorphisms have significant effects on the development of nephropathy in type 2 diabetes patients. The genes may, therefore, be considered as risk factors for Malaysian subjects who are predisposed to T2DM nephropathy.
2型糖尿病（T2DM）与肾病的高发病率相关。本研究的目的是调查肌肽酶（和）、内皮型一氧化氮合酶（）和锰超氧化物歧化酶（）基因的遗传多态性与马来西亚2型糖尿病患者糖尿病肾病发生之间的关联。采用病例对照关联研究，纳入652例T2DM患者，其中包括227名马来人（无肾病者96例，有肾病者131例）、203名华人（无肾病者95例，有肾病者108例）和222名印度人（无肾病者136例，有肾病者86例）。对的进行DNA测序，其余基因使用Sequenom MassARRAY进行检测以鉴定多态性。从T2DM患者采集的二次血样中提取DNA。使用四种遗传模型检测等位基因和基因型，并根据最小的值选择最佳遗传模式。仅在印度人中，的与糖尿病肾病显著相关，OR = 1.94，95%CI =（1.76 - 3.20），最符合乘法模型，而在所有三个主要种族中，均与糖尿病肾病相关，在基因型乘法模型中，马来人的关联性最强，OR = 2.46，95%CI =（1.48 - 4.10），华人的OR = 2.26，95%CI =（1.34 - 3.83），印度人的OR = 1.77，95%CI =（1.18 - 2.65）。和的最佳遗传模式均为加性模型。对于 - ，华人的OR = 2.8，95%CI =（0.53 - 14.94），印度人的OR = 2.4，95%CI =（0.69 - 2.84），马来人的OR = 2.16，95%CI =（0.54 - 8.65）；对于 - ，印度人的风险最高，OR = 3.16，95%CI =（0.52 - 17.56），其次是华人，OR = 3.55，95%CI =（0.36 - 35.03），马来人的OR = 2.89，95%CI =（0.29 - 28.32）。四种与氧化应激相关的多态性对2型糖尿病患者肾病的发生有显著影响。因此，对于易患T2DM肾病的马来西亚受试者，这些基因可被视为风险因素。
