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

Radiographic assessment of the postoperative knee

Radiologists often encounter postoperative knee radiographs lacking any adjunct clinical data which might hinder accurate image interpretation. Surgical techniques are constantly evolving with new devices being used which make it sometimes challenging for the radiologist to deduce the performed procedure and to look for associated complications. This article reviews commonly performed surgical procedures of the knee, highlights their expected postoperative radiographic appearance and describes the appearance of certain postoperative complications. •Postoperative knee radiographs lacking any adjunct clinical/surgical history are often encountered by radiologists.•Knowledge of common surgical procedures and their postoperative radiographic appearances helps determine the initial injury.•Familiarity with expected postoperative appearances of a knee facilitates recognition of procedure-specific complications

CHARGE syndrome:a review of the immunological aspects

CHARGE syndrome is caused by a dominant variant in the CHD7 gene. Multiple organ systems can be affected because of haploinsufficiency of CHD7 during embryonic development. CHARGE syndrome shares many clinical features with the 22q11.2 deletion syndrome. Immunological abnormalities have been described, but are generally given little attention in studies on CHARGE syndrome. However, structured information on immunological abnormalities in CHARGE patients is necessary to develop optimal guidelines for diagnosis, treatment and follow-up in these patients. Here, we provide an overview of the current literature on immunological abnormalities in CHARGE syndrome. We also explore immunological abnormalities in comparable multiple congenital anomaly syndromes to identify common immunological phenotypes and genetic pathways that might regulate the immune system. Finally, we aim to identify gaps in our knowledge on the immunological aspects in CHARGE syndrome that need further study