Peroxisome Proliferator-Activated Receptor-γ Coactivator 1-α (PPARGC1A) Genetic Associations with Type 2 Diabetes in Three Ethnicities

Genetic heterogeneity, lifestyle factors, gene-gene or gene-environment interactions are the determinants of T2D which puts Hispanics and populations with African ancestry at higher risk of developing T2D. In this dissertation, the genetic associations of PPARGC1A polymorphisms with T2D and its related phenotypes (metabolic markers) in Haitian Americans (cases=110, controls=116), African Americans (cases=120, controls=124) and Cuban Americans (cases=160, controls=181) of South Florida were explored. Five single nucleotide polymorphisms of gene PPARGC1A were evaluated in each ethnicity for their disease association. In Haitian Americans, rs7656250 (OR= 0.22, pp=0.03) had significant protective association with T2D but had risk association in African Americans for rs7656250 (OR=1.02, p=0.96) and rs4235308 (OR=2.53, p=0.03). We found that in Haitian American females, both rs7656250 (OR=0.23, pp=0.03) had protective association with T2D. In African American females, rs7656250 (OR=1.14, p=0.78) had risk association whereas in males, it had significant protective effect (OR=0.37, p=0.04). However, the risk association exhibited by rs4235308 was stronger in African American females (OR=2.69, p=0.03) than males (OR=1.16, p=0.72). In Cuban Americans, only rs7656250 showed significant risk association with T2D (OR=6.87, p=0.02) which was stronger in females alone (OR=7.67, p=0.01). We also observed significant differences among correlations of PPARGC1A SNPs and T2D phenotypes. Positive correlation was observed for log Hs-CRP with rs3774907 (pp=0.03) in Cuban Americans respectively. Correlation of log A1C with rs7656250 (p=0.02) was positive in Cuban Americans while it was negative for rs3774907 in Haitian Americans (ppPPARGC1A correlations with T2D and its phenotypes among the three ethnicities studied (ii) the associations of PPARGC1A SNPs showed significant effect modification by sex. The findings suggest that variations in effects of PPARGC1A gene polymorphisms among three ethnicities and between sexes may have biomedical implications for the development of T2D as well as the phenotypes related to T2D.

*Adoption status: A risk factor or protective factor for children of divorced families

This study examined two competitive hypotheses: the double jeopardy hypothesis and the buffering effect hypothesis on whether parental divorce affects adopted children and non-adopted children similarly or differently. The double jeopardy hypothesis suggests that when adopted children experience their parents' divorce, they perform worse because they carry two risk factors, adoption status and parental divorce, while their non-adopted counterparts carry only the risk factor of their parents' divorce. The buffering effect hypothesis suggests that, being adopted children, their previous experiences of parental loss help them better deal with the later loss of their parents' divorce so their adoption status is a protective factor rather than a risk factor. ^ Secondary analyses of a nation-wide data set were executed using different statistical methods such as ANOVA and Chi-square on different outcome variables. The results indicated that there was no evidence supporting the double-jeopardy hypothesis. That is, adopted children from divorced families did not perform significantly worse than the non-adopted children from divorced families on any outcome variable. The results also indicated that there was only weak evidence supporting the buffering effect hypothesis. The general conclusion based on the results from most of the outcome variables suggest that adopted children from divorced families do not perform differently than the biological children from divorced families. ^