Genetic Diversity of Insulin Resistance and Metabolic Syndrome

*Sanghoo Lee, Jinwoo Ahn, Jimyeong Park, Hyeonkyun Na, Youngkee Lee, Yejin Kim, Gayeon Hong and Kyoung-Ryul Lee*

## **Abstract**

A key in the etiology of a cluster of metabolic syndrome such as hyperglycemia, dyslipidemia, and obesity is known for insulin resistance, which is becoming a major global public health problem. Extensive studies have revealed many genetic factors for both insulin resistance and the components of metabolic syndrome. Advanced modern genotyping methods including genome-wide association studies and next-generation sequencing have allowed for the identification of both common and rare genetic variants related to these chronic disease-associated traits. Multiple genotype–phenotype studies are also needed to identify new and accurate genetic biomarkers in these conditions. The purpose of this chapter is to present genetic variants related to the pathogenesis of metabolic syndrome and insulin resistance and is to review the relevance between insulin resistance and metabolic syndrome clusters in terms of genetic diversity.

**Keywords:** metabolic disorders, genetic variation, genetic biomarker, genetic analysis

### **1. Introduction**

Metabolic syndrome (MetS), known as syndrome X, Deadly Quartet, or insulin resistance syndrome is characterized by a cluster of metabolic risk factors such as obesity, hypertension, dyslipidemia, and elevated fasting plasma glucose [1]. The metabolic risk factors can result in type 2 diabetes (T2D) and cardiovascular disease (CVD) that are due to both genetic and environmental factors [2, 3]. For these reasons, MetS is becoming a global epidemic. The prevalence of MetS is estimated at 11.9–37.1% in Asia-Pacific region [4], 11.6–26.3% in Europe [5], and 22–24% in North America [6].

One of the primary mediators of MetS is known for insulin resistance (IR), which is a pathological state of improper cellular response to the hormone insulin in insulin-dependent cells such as skeletal muscle and adipose tissue [7]. IR is present in the majority of people with many metabolic disorders such as MetS and T2D. IR plays a crucial role in the pathophysiology of both T2D and CVD [7] but inversely related to insulin sensitivity in insulin-dependent tissues [8]. Clinical risk factors such as obesity, dyslipidemia, inflammation, hyperinsulinemia, and dysglycemia are also known to affect IR.

Although environmental factors such as lifestyle and socioeconomic status contribute to the development of IR and MetS, both IR and MetS are also being determined by genetic factors, as strongly evidenced by early familial genetic studies [9–11]. Based on these studies, advanced genetic analysis technologies such as genome-wide association studies (GWAS) and next-generation sequencing (NGS) are extensively being used to identify both common and rare genetic variants related to these metabolic disorder-associated traits.

This chapter is to present an overview of genetic variants involved in the pathogeneses of MetS and IR and to review the relevance between IR and MetS clusters in terms of genetic diversity.
