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

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.

[1]  T. Saruta,et al.  Novel resistin promoter polymorphisms: association with serum resistin level in Japanese obese individuals. , 2004, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[2]  N. Laird,et al.  Meta-analysis in clinical trials. , 1986, Controlled clinical trials.

[3]  H. Sul,et al.  Dominant inhibitory adipocyte-specific secretory factor (ADSF)/resistin enhances adipogenesis and improves insulin sensitivity. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[4]  B. Dallapiccola,et al.  An ATG repeat in the 3'-untranslated region of the human resistin gene is associated with a decreased risk of insulin resistance. , 2002, The Journal of clinical endocrinology and metabolism.

[5]  C. Hennekens,et al.  Design of Physicians' Health Study II--a randomized trial of beta-carotene, vitamins E and C, and multivitamins, in prevention of cancer, cardiovascular disease, and eye disease, and review of results of completed trials. , 2000, Annals of epidemiology.

[6]  C. Fox,et al.  Association of Variants in RETN With Plasma Resistin Levels and Diabetes-Related Traits in the Framingham Offspring Study , 2009, Diabetes.

[7]  Muxun Zhang,et al.  Roles of adipocyte derived hormone adiponectin and resistin in insulin resistance of type 2 diabetes. , 2006, World journal of gastroenterology.

[8]  Y. Tabara,et al.  Resistin SNP-420 determines its monocyte mRNA and serum levels inducing type 2 diabetes. , 2005, Biochemical and biophysical research communications.

[9]  Brian H Chen,et al.  Circulating Levels of Resistin and Risk of Type 2 Diabetes in Men and Women: Results From Two Prospective Cohorts , 2009, Diabetes Care.

[10]  J. Manson,et al.  Vitamin E and Risk of Type 2 Diabetes in the Women’s Health Study Randomized Controlled Trial , 2006, Diabetes.

[11]  M. Reilly,et al.  An Inflammatory Cascade Leading to Hyperresistinemia in Humans , 2004, PLoS medicine.

[12]  Kazuya Yamada,et al.  The G/G genotype of a resistin single-nucleotide polymorphism at -420 increases type 2 diabetes mellitus susceptibility by inducing promoter activity through specific binding of Sp1/3. , 2004, American journal of human genetics.

[13]  S. O’Rahilly,et al.  Resistin / Fizz3 expression in relation to obesity and peroxisome proliferator-activated receptor-gamma action in humans. , 2001, Diabetes.

[14]  Nancy R Cook,et al.  Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. , 2002, The New England journal of medicine.

[15]  M. Lazar,et al.  The hormone resistin links obesity to diabetes , 2001, Nature.

[16]  M. Kasuga,et al.  Frequency of the G/G Genotype of Resistin Single Nucleotide Polymorphism at −420 Appears to Be Increased in Younger-Onset Type 2 Diabetes , 2007, Diabetes.

[17]  M. Lazar,et al.  Regulation of Fasted Blood Glucose by Resistin , 2004, Science.

[18]  Y. M. Cho,et al.  Common genetic polymorphisms in the promoter of resistin gene are major determinants of plasma resistin concentrations in humans , 2004, Diabetologia.

[19]  浅野 展行.  Plasma resistin concentration determined by common variants in the resistin gene and associated with metabolic traits in an aged Japanese population , 2010 .

[20]  F. Hu,et al.  Total and High-Molecular-Weight Adiponectin and Resistin in Relation to the Risk for Type 2 Diabetes in Women , 2008, Annals of Internal Medicine.

[21]  Y. Kesäniemi,et al.  Resistin polymorphisms are associated with cerebrovascular disease in Finnish Type 2 diabetic patients , 2005, Diabetic medicine : a journal of the British Diabetic Association.

[22]  N. Cook,et al.  Baseline characteristics of participants in the Women's Health Study. , 2000, Journal of women's health & gender-based medicine.

[23]  Ose,et al.  Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events* , 2002 .

[24]  K. Kohara,et al.  PPARγ Pro12Ala Pro/Pro and resistin SNP‐420 G/G genotypes are synergistically associated with plasma resistin in the Japanese general population , 2009, Clinical endocrinology.

[25]  J. Manson,et al.  A prospective study of red meat consumption and type 2 diabetes in middle-aged and elderly women: the women's health study. , 2004, Diabetes care.

[26]  R. N. Bergman,et al.  Variation in the resistin gene is associated with obesity and insulin-related phenotypes in Finnish subjects , 2004, Diabetologia.