Parchwani Deepak, Dholariya Sagar, Patel Digishaben D, Agravatt Ashishkumar, Uperia Jayant, Parchwani Tanishk, Singh Ragini, Radadiya Madhuri, Desai Yash
All India Institute of Medical Sciences, Rajkot, Gujarat India.
BJ Medical College, Ahmedabad, Gujarat India.
Indian J Clin Biochem. 2023 Oct;38(4):505-511. doi: 10.1007/s12291-022-01065-5. Epub 2022 Aug 9.
Phenotypic expression of metabolic syndrome is precipitated by environmental variables along with the individual genetic susceptibility to the obesogenic environment and growing body of evidence suggest a paramount role of adipocytokines. Therefore, identifying the genetic influence on circulation leptin levels and clarifying genotype-phenotype correlation of rs1137101 {Leptin receptor gene (LEPR) Gln223Arg (Q223R; A668G)} in metabolic syndrome were the primary objective of this study. A total of 447 adult participants, including 214 metabolic syndrome patients and 233 healthy controls, were genotyped using polymerase chain reaction-restriction fragment length polymorphism method to unravel the effects of genetic risk loci {Leptin receptor gene; Gln223Arg (Q223R; A668G); rs1137101} on the occurrence of metabolic syndrome in consort with circulation leptin levels. Suitable descriptive statistics was used for different variables. The genotype frequencies were found to be in Hardy-Weinberg equilibrium for both cases (p > 0.2722) as well as in controls (p > 0.2331). However, genotype (x2: 11.26, 2 d.f. p = 0.0036) and allele distribution (x2: 10.51, 2 d.f. p: 0.0012) of the LEPR Gln223Arg (Q223R; A668G) differed significantly between cases and controls. Gln/Arg genotype (OR = 1.6099; 95% CI = 1.0847-2.3893; p value = 0.0181), Arg/Arg genotype (OR = 2.8121; 95% CI = 1.4103-5.6074; p value = 0.0033) and R allele (OR = 1.5875; 95% CI = 1.1996-2.1008; p value = 0.0012) were significantly associated with increased risk of metabolic syndrome in univariate analysis. Further a multivariate logistic regression adjusted for potential confounders showed that Arg/Arg genotype (OR = 1.9; 95% CI = 1.271-2.639; p-value < 0.05) and Gln/Arg (OR: 1.3; 95% CI = 0.873-2.034; p value < 0.05) have a significant risk for the occurrence of the metabolic syndrome. A progressive increase in the serum leptin levels from major homozygous alleles to minor homozygous alleles were observed indicating that rs1137101 modify the serum leptin concentrations in patients with metabolic syndrome. These findings provide enough evidence of a significant association of LEPR Gln223Arg (Q223R; A668G) polymorphism in the LepR gene in Indian patients with increased risk of metabolic syndrome for R allele and Arg/Arg homozygote. Thus, rs1137101 might be a pleiotropic locus for metabolic syndrome and its components in studied population.
代谢综合征的表型表达是由环境变量以及个体对致肥胖环境的遗传易感性共同促成的，越来越多的证据表明脂肪细胞因子起着至关重要的作用。因此，本研究的主要目的是确定遗传因素对循环瘦素水平的影响，并阐明rs1137101（瘦素受体基因（LEPR）Gln223Arg（Q223R；A668G））在代谢综合征中的基因型与表型的相关性。共有447名成年参与者，包括214名代谢综合征患者和233名健康对照，采用聚合酶链反应-限制性片段长度多态性方法进行基因分型，以揭示遗传风险位点（瘦素受体基因；Gln223Arg（Q223R；A668G）；rs1137101）与循环瘦素水平对代谢综合征发生的影响。对不同变量采用了适当的描述性统计方法。发现病例组（p＞0.2722）和对照组（p＞0.2331）的基因型频率均处于哈迪-温伯格平衡。然而，LEPR Gln223Arg（Q223R；A668G）的基因型（x2：11.26，自由度为2，p = 0.0036）和等位基因分布（x2：10.51，自由度为2，p：0.0012）在病例组和对照组之间存在显著差异。在单因素分析中，Gln/Arg基因型（OR = 1.6099；95% CI = 1.0847 - 2.3893；p值 = 0.0181）、Arg/Arg基因型（OR = 2.8121；95% CI = 1.4103 - 5.6074；p值 = 0.0033）和R等位基因（OR = 1.5875；95% CI = 1.1996 - 2.1008；p值 = 0.0012）与代谢综合征风险增加显著相关。进一步进行多因素逻辑回归分析，对潜在混杂因素进行校正后显示，Arg/Arg基因型（OR = 1.9；95% CI = 1.271 - 2.639；p值＜0.05）和Gln/Arg（OR：1.3；95% CI = 0.873 - 2.034；p值＜0.05）对代谢综合征的发生具有显著风险。观察到血清瘦素水平从主要纯合子等位基因到次要纯合子等位基因呈逐渐升高趋势，表明rs1137101可改变代谢综合征患者的血清瘦素浓度。这些发现充分证明了印度患者中LepR基因的LEPR Gln223Arg（Q223R；A668G）多态性与R等位基因和Arg/Arg纯合子的代谢综合征风险增加显著相关。因此，在研究人群中，rs1137101可能是代谢综合征及其组分的一个多效性位点。
