Chemokine gene polymorphisms association with increased risk of type 2 diabetes mellitus in Tatar ethnic group, Russia
MOLECULAR BIOLOGY REPORTS
Authors: Kochetova, Olga V.; Avzaletdinova, Diana S.; Morugova, Tatyana V.; Mustafina, Olga E.
Abstract
Recent studies have shown that chemokines play an important role in the development of chronic inflammation in adipose tissue, obesity pathogenesis, glucose intolerance and type 2 diabetes. It has also been revealed that some SNPs in chemokine genes are associated with obesity, insulin resistance, type 2 diabetes and diabetes complications in different ethnic groups. The aim of this study was to determine the associations between SNPs in chemokine genes and type 2 diabetes in participants of Tatar ethnic group, living in Bashkortostan. Case-control and cross-sectional study were included in our study design. Five SNPs were genotyped in 440 type 2 diabetes (160 men and 280 women), 58.8 +/- 9.2 years old (mean +/- SD), BMI 29.3 +/- 3.9 kg/m(2) (mean +/- SD) patients of Tatar ethnicity, and a control group of 500 Tatars (180 men and 320 women), 55.2 +/- 11.6years old (mean +/- SD), BMI 25.9 +/- 4.3 kg/m(2) (mean +/- SD). The SNPs rs6749704 in CCL20 [odds ratio (OR)=2.77 (95% CI 1.81-4.25), p=0.0001], rs2107538 in CCL5 [odds ratio (OR)=1.80 (95% CI 1.46-2.22), p=0.0001] were significantly associated with type 2 diabetes. Regression analysis revealed that rs1696941 in CCL11 was associated with the onset age and duration of type 2 diabetes as well as with HbA(1c) level (p=0.034, p=0.036 and p=0.0054, respectively). The SNPs rs223828 in CCL17 and rs6749704 in CCL20 were correlated with obesity as estimated by BMI (p=0.0004, p=0.029, respectively). Rs223828 in CCL17 revealed the association with postprandial glucose level (p=0.024) and HbA(1c) (p=0.008). These data demonstrate that variants of chemokine genes are associated with type 2 diabetes and obesity of Tatar ethnic group inhabiting Bashkortostan Republic. Novel associations of the polymorphic loci in CCL20 (rs6749704) and CCL5 (rs2107538) genes with type 2 diabetes had been identified as a result of the conducted research.
Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome
MOLECULAR PSYCHIATRY
Authors: Hornig, M.; Gottschalk, G.; Peterson, D. L.; Knox, K. K.; Schultz, A. F.; Eddy, M. L.; Che, X.; Lipkin, W. I.
Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome is an unexplained debilitating disorder that is frequently associated with cognitive and motor dysfunction. We analyzed cerebrospinal fluid from 32 cases, 40 subjects with multiple sclerosis and 19 normal subjects frequency-matched for age and sex using a 51-plex cytokine assay. Group-specific differences were found for the majority of analytes with an increase in cases of CCL11 (eotaxin), a chemokine involved in eosinophil recruitment. Network analysis revealed an inverse relationship between interleukin 1 receptor antagonist and colony-stimulating factor 1, colony-stimulating factor 2 and interleukin 17F, without effects on interleukin 1 alpha or interleukin 1 beta, suggesting a disturbance in interleukin 1 signaling. Our results indicate a markedly disturbed immune signature in the cerebrospinal fluid of cases that is consistent with immune activation in the central nervous system, and a shift toward an allergic or T helper type-2 pattern associated with autoimmunity.