Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara, 390002, Gujarat, India.
Human Genetics Research Group, School of Biotechnology, S.M.V.D.U, Katra, 182320, Jammu and Kashmir, India.
Sci Rep. 2020 Feb 19;10(1):2904. doi: 10.1038/s41598-020-59845-z.
Adiponectin is a prime determinant of the status of insulin resistance. Association studies between adiponectin (ADIPOQ) gene single nucleotide polymorphisms (SNPs) and metabolic diseases have been reported earlier. However, results are ambiguous due to apparent contradictions. Hence, we investigated (1) the association between ADIPOQ SNPs: -11377C/G, +10211T/G, +45T/G and +276G/T for the risk towards type 2 diabetes (T2D) and, (2) genotype-phenotype association of these SNPs with various biochemical parameters in two cohorts. Genomic DNA of diabetic patients and controls from Gujarat and, Jammu and Kashmir (J&K) were genotyped using PCR-RFLP, TaqMan assay and MassArray. Transcript levels of ADIPOQ were assessed in visceral adipose tissue samples, and plasma adiponectin levels were estimated by qPCR and ELISA respectively. Results suggest: (i) reduced HMW adiponectin/total adiponectin ratio in Gujarat patients and its association with +10211T/G and +276G/T, and reduced ADIPOQ transcript levels in T2D, (ii) association of the above SNPs with increased FBG, BMI, TG, TC in Gujarat patients and (iii) increased GGTG haplotype in obese patients of Gujarat population and, (iv) association of -11377C/G with T2D in J&K population. Reduced HMW adiponectin, in the backdrop of obesity and ADIPOQ genetic variants might alter metabolic profile posing risk towards T2D.
脂联素是胰岛素抵抗状态的主要决定因素。先前已经有研究报道过脂联素（ADIPOQ）基因单核苷酸多态性（SNP）与代谢性疾病之间的关联。然而，由于明显的矛盾，结果仍存在争议。因此，我们在两个队列中研究了（1）ADIPOQ SNP：-11377C/G、+10211T/G、+45T/G 和 +276G/T 与 2 型糖尿病（T2D）风险之间的关联，以及（2）这些 SNP 与各种生化参数的基因型-表型关联。使用 PCR-RFLP、TaqMan 检测和 MassArray 对来自古吉拉特邦和查谟和克什米尔邦（J&K）的糖尿病患者和对照者的基因组 DNA 进行基因分型。通过 qPCR 和 ELISA 分别评估内脏脂肪组织样本中的 ADIPOQ 转录水平和血浆脂联素水平。结果表明：（i）古吉拉特邦患者的高分子量脂联素/总脂联素比值降低，与 +10211T/G 和 +276G/T 相关，T2D 患者的 ADIPOQ 转录水平降低，（ii）上述 SNP 与古吉拉特邦患者的 FBG、BMI、TG、TC 增加相关，（iii）古吉拉特邦肥胖患者的 GGTG 单倍型增加，以及（iv）-11377C/G 与 J&K 人群中的 T2D 相关。在肥胖和 ADIPOQ 遗传变异的背景下，高分子量脂联素的减少可能会改变代谢特征，增加 T2D 的风险。
