Monocyte chemoattractant protein-1 gene polymorphism and its serum level have an impact on anthropometric and biochemical risk factors of metabolic syndrome in Indian population A. K. Madeshiya*, S. Singh*, S. Dwivedi*, K. S. Saini † , R. Singh ‡ , S. Tiwari*, R. Konwar † & A. Ghatak § Summary Monocyte chemoattractant protein-1 (MCP-1), encoded by gene CCL-2 (Chemokine C-C motif 2), is the ligand of chemokine receptor CCR-2. Concurrent clinical alteration in several metabolic aspects, including central obesity, dysglycemia, dyslipidemia and hypertension, is clinically characterized as metabolic syndrome (MetS). Role of MCP-1 in each of these aspects has been estab- lished in vitro and in animal studies as well. We here report genetic association of 2518 A>G MCP-1 (rs 1024611) gene polymorphism and level of MCP-1 with MetS in North Indian subjects. We analysed (n = 386, controls and n = 384, MetS subjects) for MCP-1 gene polymorphism using PCR-RFLP, its serum level using ELISA, anthropometric (body mass index, waist and hip circumferences, waist–hip ratio and blood pressure) and biochemical (serum lipids, plasma glucose and insulin levels) variables in a genetic association study. The body mass index, waist circumference, hip circumference, waist–hip ratio, blood pressure, serum lipids, insulin and fasting plasma glucose level were significantly high in MetS subjects. Regression analysis showed significant correlation of body mass index, waist and hip circum- ference, systolic/diastolic blood pressure, fasting glucose, total cholesterol, high-density lipoprotein, low- density lipoprotein fasting insulin and HOMA-IR with MetS. MCP-1 allele and genotype were significantly associated with MetS. Serum MCP-1 level was high in overall cases. In conclusions, the MCP-1 2518A>G (rs 1024611) polymorphism has significant impact on risk of MetS, and MCP-1 level correlates with anthropomet- ric and biochemical risk factors of MetS. Introduction MetS, earlier known as ‘insulin resistance syndrome’ is the clustering of cardiovascular risk factors such as abdominal obesity, hypertension, dyslipidemia and glucose intolerance in the patient (Groop, 2000). Sev- eral definitions of MetS are available, but National Cholesterol Education Program (NCEP) Adult Treat- ment Panel-III guideline’s definition is most widely accepted (Kassi et al., 2011). However, it is debatable as some studies suggest that the current definition of MetS may not capture all cardiovascular risks, particu- larly associated with insulin resistance (Rutter et al., 2005). Undoubtedly, global prevalence of the MetS is rapidly increasing (Cameron et al., 2004). Several studies in India also indicated the prevalence of the insulin resistance and MetS range from about 11–41% depending on the region and degree of urbanization (Misra & Vikram, 2002). A recent study showed that almost 1/3rd of the urban population in major metro- politan cities in India had MetS (Vikram et al., 2006). MCP-1, a chemokine produced predominantly by macrophages and endothelial cells, is a potent chemo- tactic factor for monocytes (Yoshimura et al., 1989). Role of inflammation in the pathogenesis and progres- sion of metabolic diseases and involvement of MCP-1 in these events is well recognized. Over the past few decades, overwhelming evidence has accumulated that supports the key role of MCP-1 in the development of atherosclerosis (Gerszten et al., 2000). MCP-1 recruits monocytes to sites of inflammation playing an important role in atherosclerosis. MCP-1 level also increases in diabetes and insulin resistance. Obesity is associated with increased adipose tissue infiltration by macrophages and activated macrophages in the adi- pose tissue secrete MCP-1. Several studies indicate that MCP-1-mediated macrophage infiltration of adipose tissue may contribute to the metabolic *Department of Physiology, King George’s Medical University, Luc- know, India, † Division of Endocrinology, Central Drug Research Insti- tute, Lucknow, India, ‡ ESI Hospital, Lucknow, India and § Division of Clinical and Experimental Medicine, Central Drug Research Institute, Lucknow, India Received 3 July 2014; revised 22 September 2014; accepted 14 December 2014 Correspondence: Shraddha Singh, Department of physiology, King George’s Medical University, Lucknow, India. Tel: +91 9415010703; Fax: +91-0522-2257539/2258440; E-mail: dr.shraddha22@rediffmail. com © 2015 John Wiley & Sons Ltd 78 International Journal of Immunogenetics, 2015, 42, 78–86 doi: 10.1111/iji.12174