Genetic Variants at the Resistin Locus and Risk of Type 2 Diabetes in Caucasians
Xiaowei Ma,
James H. Warram,
Vincenzo Trischitta and
Alessandro Doria
Section on Genetics and Epidemiology, Research Division, Joslin Diabetes Center (X.M., J.H.W., A.D.), and Department of Medicine, Harvard Medical School (X.M., A.D.), Boston, Massachusetts 02215; Unit of Endocrinology, Ospedale Casa Sollievo della Sofferenza (E.T.), 71013 San Giovanni Rotondo, Italy; and Department of Clinical Science, University La Sapienza (E.T.), 00161 Rome, Italy
Address all correspondence and requests for reprints to: Alessandro Doria, M.D., Ph.D., Section on Genetics, Epidemiology, Joslin Diabetes Center, One Joslin Place, Boston, Massachusetts 02215. E-mail: . alessandro.doria{at}joslin.harvard.edu
Abstract
Resistin is a newly identified hormone secreted by adipocytesthat inhibits insulin action on peripheral tissues. The aimof our study was to investigate whether genetic variabilityat this locus is associated with the risk of type 2 diabetes.By sequencing 32 subjects with type 2 diabetes, we identified8 single nucleotide polymorphisms (SNPs) in the 5'-flankingregion and introns of the resistin gene. Allele and genotypedistributions were determined for all 8 SNPs in 312 cases withtype 2 diabetes and 303 nondiabetic controls, all of Caucasianorigin. No significant association with type 2 diabetes wasfound at any of the polymorphic loci. However, an interactiveeffect of genotype at SNP 6 (IVS2 + 181GA) and obesity was asignificant determinant of type 2 diabetes risk in this population.The relative risk of diabetes for the A/A genotype was 4.8 (95%confidence interval, 1.1–21.0) in individuals above themedian for body weight, but only 0.7 (95% confidence interval,0.2–2.1) in those below the median. This difference betweenrelative risks was significant (2 = 4.5; P = 0.03). A similar,but much weaker, interaction with obesity was observed for SNPsin linkage disequilibrium with SNP6. In conclusion, resistindoes not appear to be a major gene for type 2 diabetes. However,our data suggest a synergistic effect of sequence differencesat the resistin locus and obesity on risk of type 2 diabetes.Further studies are needed to confirm this finding in otherpopulations.
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A) and obesity was a significant determinant of type 2 diabetes risk in this population. The relative risk of diabetes for the A/A genotype was 4.8 (95% confidence interval, 1.1–21.0) in individuals above the median for body weight, but only 0.7 (95% confidence interval, 0.2–2.1) in those below the median. This difference between relative risks was significant (
2 = 4.5; P = 0.03). A similar, but much weaker, interaction with obesity was observed for SNPs in linkage disequilibrium with SNP6. In conclusion, resistin does not appear to be a major gene for type 2 diabetes. However, our data suggest a synergistic effect of sequence differences at the resistin locus and obesity on risk of type 2 diabetes. Further studies are needed to confirm this finding in other populations. 
