Original Article Association of resistin promoter polymorphisms with plasma resistin levels and type 2 diabetes in women and men

Brian Chen, Yiqing Song, Eric Ding, Joann Manson, Christian Roberts, Nader Rifai, Julie Buring, J Gaziano, Simin Liu
2010 J Mol Epidemiol Genet   unpublished
Introduction The clinical and biological significance of the adipokine resistin in the development of type 2 diabetes remains uncertain. Current evidence from animal models indicates that a reduction in functional resistin protein (via gene knockout , anti-resistin immunoglobulin, and dominant inhibition) can lower blood glucose levels and improve insulin sensitivity [1-3]. In addition, elevated levels of serum resistin in diabetic db/ db mice implicate resistin as a key mediator between
more » ... ator between adiposity and type 2 diabetes [3]. In humans, circulating resistin levels are higher among individuals with type 2 diabetes than among apparently healthy individuals [4-6]. Recently , two prospective cohort studies related baseline resistin levels to future development of type 2 diabetes, although this relation appeared to be mediated, in part, by BMI[4, 5] or inflam-matory markers [4]. The suggestion of inflam-matory pathway involvement is consistent with the fact that mononuclear cells are the primary source of resistin in humans [7]. In contrast, the causal relation between resistin levels and adi-posity in humans remains unclear. Resistin lev-Int Abstract: This study's objective was to examine the associations between resistin (RETN) polymorphisms, plasma resistin levels, and type 2 diabetes risk. We conducted two nested case-control studies in postmenopausal women (359 incident cases and 359 controls) and middle-aged/elderly men (170 incident cases and 170 controls). Controls were matched (1:1) to cases by age, race, duration of follow-up, and time of blood draw. Circulating resistin levels were higher among carriers of the variant allele for rs34861192 (p<0.0001 for women, p=0.002 for men) but not rs1862513 (p=0.15 for women, p=0.14 for men). Neither polymorphism was significantly associated with risk of type 2 diabetes after adjusting for diabetes risk factors (exercise, smoking status, alcohol intake, family history of diabetes , and matching factors) among women (rs1862513: OR=1.19, 95% CI=0.80-1.77; rs34861192: OR=0.41, 95% CI=0.14-1.19) and men (rs1862513: OR=1.05, 95% CI=0.57-1.95; rs34861192: OR=0.64, 95% CI=0.14-2.89). In conclusion, RETN promoter polymorphism rs34861192 was associated with elevated circulating resistin levels, but rs1862513 was not. Neither polymorphism was associated with an increased risk for type 2 diabetes.