EMMRC, Anna University Campus, Guindy, Chennai 600 025, Tamil Nadu, India.
Department of Genetics, Dr. ALM PG Institute of Basic Medical Science, University of Madras, Tamilnadu, India.
J Diabetes Complications. 2022 Jan;36(1):108074. doi: 10.1016/j.jdiacomp.2021.108074. Epub 2021 Oct 8.
Circulatory Fetuin-A has been well reported to elevate the risk for Diabetic Nephropathy (DN) and is associated with many vascular complications. Compelling reports have well documented that the circulatory levels of Fetuin-A directly have an impact on its AHSG (α2- Heremans- Schmid Glycoprotein) gene single nucleotide polymorphisms (SNP). Thus, in this study among the South Indian T2DM population, we aim to explore the association of AHSG Thr256Ser (rs4918) SNP in subjects with DN and correlate with the circulatory levels of Fetuin-A at various stages of DN patients.
A total of 975 subjects were recruited, such as Group-I, consisting of Controls (n = 300), Group-II, with normoalbuminuria (n = 300), Group-IIIa, with incipient microalbuminuria (n = 195), Group-IIIb, with persistent macroalbuminuria (n = 180)] and were subjected for genotyping using PCR-Restriction Fragment Length Polymorphism (RFLP). Circulatory Fetuin-A was measured using sandwich enzyme-linked immunosorbent assay (ELISA).
The 'G' allele of AHSG exon-7 (C/G) SNP is significantly concomitant and conferred significant risk for normoalbuminuria subjects. In the DN subjects, the 'G' allele showed the risk for persistent macroalbuminuria. A noticeable stepwise decrease was evidenced in the circulatory Fetuin-A among persistent macroalbuminuria over incipient microalbuminuria from normoalbuminuria. Further, the circulatory Fetuin-A was lowered in DN subjects with mutant GG genotype than the wild CC.
AHSG Thr256Ser (rs4918) SNP was associated with renal complications among South Indian T2DM subjects.
循环 Fetuin-A 已被充分报道可增加糖尿病肾病 (DN) 的风险，并且与许多血管并发症相关。令人信服的报告充分证明，循环 Fetuin-A 的水平直接影响其 AHSG（α2-赫曼斯-施密特糖蛋白）基因单核苷酸多态性 (SNP)。因此，在这项针对南印度 T2DM 人群的研究中，我们旨在探讨 AHSG Thr256Ser(rs4918) SNP 在患有 DN 的受试者中的相关性，并与 DN 患者各个阶段的循环 Fetuin-A 水平相关。
共招募了 975 名受试者，如第 I 组，包括对照组（n=300）、第 II 组，正常白蛋白尿（n=300）、第 IIIa 组，微量白蛋白尿初期（n=195）、第 IIIb 组，持续大量白蛋白尿（n=180），并使用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）进行基因分型。使用夹心酶联免疫吸附测定法（ELISA）测量循环 Fetuin-A。
AHSG 外显子 7（C/G）SNP 的 'G' 等位基因与正常白蛋白尿受试者显著相关，并赋予其显著的风险。在 DN 受试者中，'G' 等位基因显示出持续大量白蛋白尿的风险。在从正常白蛋白尿到微量白蛋白尿初期的持续大量白蛋白尿中，循环 Fetuin-A 明显呈阶梯式下降。此外，与野生 CC 基因型相比，DN 受试者的突变 GG 基因型的循环 Fetuin-A 降低。
AHSG Thr256Ser(rs4918) SNP 与南印度 T2DM 受试者的肾脏并发症相关。
