Association of CLOCK gene variants with obesity and adiposity-related anthropometric, metabolic, and behavioral parameters

Abstract

The CLOCK gene is a core component of the circadian clock and regulates various aspects of metabolism. Therefore, any variation that affects the function/expression of the CLOCK gene may contribute to the manifestation of metabolic disorders such as obesity. This study investigated whether the CLOCK variants rs4864548 and rs6843722 are associated with obesity and related traits in Pakistanis. A total of 306 overweight/obese cases and 306 age- and gender-matched control subjects were recruited (males 336 and females 276, age range 12–63 years). Anthropometric and metabolic parameters were taken by standard procedures and biochemical analyses, respectively. Behavior-related information was collected with a questionnaire. The genotypes of the variants were determined by allelic discrimination Taqman assays. Both variants were found to have a significant association with overweight/obesity according to the over-dominant model. The rs4864548 and rs6843722 were observed to escalate the risk of overweight/obesity by 1.611 ( p = 0.004) and 1.657 ( p = 0.002) times, respectively. These variants were also seen to be significantly associated with various other adiposity-related anthropometric parameters ( p < 0.05). However, no association of both variants with metabolic and behavioral parameters was observed ( p > 0.05). Thus, these variants may contribute to increasing the risk of overweight/obesity and related anthropometric traits in Pakistanis.