PURPOSE OF REVIEW

To provide a brief review of methods used in genetic epidemiology studies, an update of recent significant findings in genome-wide studies of kidney disease, and a discussion of the clinical implications of these findings.

RECENT FINDINGS

Recent developments in genetic epidemiology methodologies, specifically the use of genome-wide panels of single nucleotide polymporphisms (SNPs) for association analyses, have yielded exciting insights into the underlying pathogenesis of chronic kidney disease and its progression. The two most notable and promising genetic discoveries are those of MYH9 and UMOD, both of which have been replicated in separate populations.

SUMMARY

Genomic studies have the potential to yield exciting new areas of biological research, potential targets for treatment, and ultimately markers of disease risk. This review addresses recent genetic studies and their implications in chronic kidney disease care.

OBJECTIVES

We explored whether the United States, which does not regulate pharmaceutical prices, is responsible for the development of a disproportionate share of the new molecular entities (NMEs; a drug that does not contain an active moiety previously approved by the Food and Drug Administration) produced worldwide.

METHODS

We collected data on NMEs approved between 1992 and 2004 and assigned each NME to an inventor country. We examined the relation between the proportion of total NMEs developed in each country and the proportion of total prescription drug spending and gross domestic product (GDP) of each country represented.

RESULTS

The United States accounted for 42% of prescription drug spending and 40% of the total GDP among innovator countries and was responsible for the development of 43.7% of the NMEs. The United Kingdom, Switzerland, and a few other countries innovated proportionally more than their contribution to GDP or prescription drug spending, whereas Japan, South Korea, and a few other countries innovated less.

CONCLUSIONS

Higher prescription drug spending in the United States does not disproportionately privilege domestic innovation, and many countries with drug price regulation were significant contributors to pharmaceutical innovation.

Previous work has suggested that an extracellular matrix degrading enzyme-matrix metalloproteinase-2 (MMP-2) plays an important role in the development of muscle atrophy. However, the transcriptional regulation mechanism of MMP-2 in skeletal muscle atrophy remains largely unknown. Using transgenic MMP-2 promoter reporter mice, we have demonstrated that AP-1 and RE-1 binding sites in the MMP-2 promoter region, coupled with increased binding of Fra-1, Fra-2 and AP-2, play a critical role in MMP-2 transcriptional regulation in muscle atrophy. Novel information gained from this study has improved our understanding of in vivo transcriptional regulation of MMP-2 in skeletal muscle atrophy.