Common Variants of Inflammatory Cytokine Genes Are Associated with Risk of Nephropathy in Type 2 Diabetes among Asian Indians

BACKGROUND: Inflammatory cytokine genes have been proposed as good candidate genes for conferring susceptibility to diabetic nephropathy. In the present study, we examined the combined effect of multiple alleles of pro inflammatory cytokine genes for determining the risk of nephropathy in type 2 diabetic patients. METHODOLOGY/PRINCIPAL FINDINGS: Eight single nucleotide polymorphisms (SNPs) of pro-inflammatory cytokine genes (CCL2, TGFB1, IL8, CCR5, and MMP9) were genotyped in two independently ascertained type 2 diabetic cohorts with (DN) and without nephropathy (DM); consisting of patients from North India (n = 495) and South India (n = 188). Genotyping was carried out using PCR, allele specific oligonucleotide-PCR (ASO-PCR), PCR-RFLP and TaqMan allelic discrimination assays and the gene-gene interaction among genetic variants were determined by multi dimensional reduction (MDR) software. Serum high sensitive CRP (hs-CRP) levels were measured by ELISA. The hs-CRP levels were significantly higher in DN as compared to the DM group (p<0.05). The CCL2, IL8, CCR5 and MMP9 polymorphisms were found to be associated with the risk of diabetic nephropathy. Frequency of CCL2 II, IL8 -251AA, CCR5 59029AA and MMP9 279Gln/Gln genotypes were significantly higher in DN than in DM group (p<0.05) and associated with an increased risk of nephropathy in both North and South Indian cohorts. CCR5 DD and IL8 -251AA genotypes were more prevalent in North Indian DN group only. The co-occurrence of risk associated genotypes (II, -2518GG (CCL2), DD (CCR5) and 279Gln/Gln (MMP9) conferred a tenfold increased risk of nephropathy among type 2 diabetics (p<0.0002). CONCLUSION: The present study highlights that common variants of inflammatory cytokine genes exert a modest effect on risk of DN and a combination of risk alleles confer a substantial increased risk of nephropathy in type 2 diabetes among Asian Indians

Alliance capability, stock market response, and long-term alliance success: the role of the alliance function

This paper addresses two key questions: (1) what factors influence firms' ability to build alliance capability and enjoy greater alliance success, where firm-level alliance success is measured in two ways: (a) abnormal stock market gains following alliance announcements and (b) managerial assessments of long term alliance performance; and (2) are the two alternate ways of assessing alliance success correlated? We find that firms with greater alliance experience and, more importantly, those that create a dedicated alliance function (with the intent of strategically coordinating alliance activity and capturing/disseminating alliance-related knowledge) realize greater success with alliances. More specifically, firms with a dedicated alliance function achieve greater abnormal stock market gains (average of 1.35%) and report that 63 percent of alliances are successful whereas firms without an alliance function achieve much lower stock market gains (average of 0.18%) and only a 50 percent long-term success rate. We also find a positive correlation between stock market-based measures of alliance success and alliance success measured through managerial assessments. In addition to providing insights into the development of alliance capability among firms, this paper is one of the first to provide empirical support for the efficient markets argument by demonstrating that the initial stock market response to a key event positively correlates to the long-term performance and value of the event. Copyright © 2002 John Wiley & Sons, Ltd.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34615/1/248_ftp.pd