Interactive Effects Of Genotype Research Articles

Genetic variants at the resistin locus and risk of type 2 diabetes in Caucasians.

Resistin is a newly identified hormone secreted by adipocytes that inhibits insulin action on peripheral tissues. The aim of our study was to investigate whether genetic variability at this locus is associated with the risk of type 2 diabetes. By sequencing 32 subjects with type 2 diabetes, we identified 8 single nucleotide polymorphisms (SNPs) in the 5'-flanking region and introns of the resistin gene. Allele and genotype distributions were determined for all 8 SNPs in 312 cases with type 2 diabetes and 303 nondiabetic controls, all of Caucasian origin. No significant association with type 2 diabetes was found at any of the polymorphic loci. However, an interactive effect of genotype at SNP 6 (IVS2 + 181G-->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 (chi(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.

Interactive effects of genotype and social environment on alcohol consumption in female twins.

Information about drinking practices has been obtained by questionnaire from 1,984 monozygotic and dizygotic adult female twin pairs from the Australian twin register, including 1,690 pairs where both twins have used alcohol. Statistical analyses of these data show that marital status is an important modifier of genetic effects on drinking habits. In young twins, aged 30 years or less, genetic differences between individuals account for only 31% of the variance in alcohol consumption of married respondents, but for 60% of the variance of unmarried respondents. In twin pairs, aged 31 years or more, genetic differences account for 46-59% of the variance in married twins, but for 76% of the variance in unmarried twins. In our young sample (average age 35 years) there is no evidence that individuals genetically predisposed to heavy drinking are any less likely to be married than the rest of the population. Some alternative explanations of these findings are also rejected.