Y regulating cytokine production [48]. Furthermore, the loss of MiR-155 leads to an overall attenuation of immune responses in mouse [49]. High CRP levels and leukocyte counts (i.e., a more severe inflammatory response) in erysipelas are associated with recurrence of erysipelas [5]. Our finding of predominance of the A-allele in our six probands is consistent with these earlier observations. Interestingly, AGTR1 and PTGES are involved in the same pathway, as AGTR1 induces the production of COX, which coverts arachidonic acid into Prostaglandin H2 that in turn is converted by PTGES into Prostaglandin E2. We found evidence for host genetic factors influencing susceptibility to bacterial non-necrotizing erysipelas/cellulitis, but did not find a common susceptibility factor in all families. We did not find linkage or association with the HLA region previously linked with GAS infection severity in humans [19,20]. It is likelyGenetic Susceptibility to Erysipelasthat as the inflammatory pathways are very complex and the defense against infections is under strong selection, different families are likely to have individual genetic susceptibilities. Genetic heterogeneity makes it difficult to find significant correlations, which is a common pitfall of studies on host genetic factors predisposing to infections. Much larger patient and control groups will be needed to verify these preliminary results. However, our linkage peak and the region of strongest association coincide with genes and pathways suggested to play important roles in susceptibility to streptococcal infections. The identification of the susceptibility genes would help to understand better the course of infections and ultimately reduce morbidity.(TIF)Table S1 Family-wise NPLall scores for the 9q34 linkage region. Families showing significant linkage are shaded dark grey. Families showing suggestive linkage are shaded light grey. (DOCX) Table SSNPs found in the family probands in AGTR1.(DOCX)AcknowledgmentsThe authors thank all 22948146 patients and families who participated in this study. Riitta Lehtinen is acknowledged for laboratory assistance, Hannu Turunen for computational assistance, Henna Degerlund, Susanna Vahakuopus, ??Maija Toropainen, Eira Leinonen, and Kirsi Kuismin for assistance in sample collection.Supporting InformationFigure S1 NPL plots for the fine mapping of the chromosome 9q34 linkage peak with 22 microsatellite markers. The NPL plots for the four configurations were essentially identical. MERLIN was used for multipoint NPL analyses using four configurations. (A) In configuration 0, unconfirmed affected individuals were analyzed as unknown, and (B) in configuration 2, they were analyzed as affected. In configurations (C) 0_186 and (D) 2_186, analysis was identical to configurations 0 and 2, respectively, except that allele 186 was called for marker D9S65.Author ContributionsManaged all patient consents and samples: PA. Conceived and designed the experiments: KHJ S. Massinen S. Makela JK JS JV TS MK. ??Performed the experiments: KHJ S. Massinen S. Makela RL KK HJ. ??Analyzed the data: KHJ S. Massinen S. Makela RL KK HJ TS MK JS JV ??JK. Contributed reagents/materials/analysis tools: JK JS JV MK PA HJ. Wrote the paper: KHJ S. Massinen TS JK.
Diseases caused by different Vibrio species have been observed in large populations throughout the world, particularly in Asia, the United States, and Africa [1?]. V. cholera and V. parahaemolyticus are the major etiological agents of v.
