VEGF Polymorphisms are not associated with an Increased Risk of Developing Renal Cell Carcinoma in Spanish population.

Hum Immunol. 2012 Oct 13;

Authors: Sáenz-López P, Vazquez F, Cozar JM, Carretero R, Garrido F, Ruiz-Cabello F

Abstract
PURPOSE: Vascular endothelial growth factor (VEGF) plays a central role in promoting angiogenesis and is over-expressed in renal cell cancer (RCC). Published data on the association between polymorphisms of vascular endothelial growth factor (e.g., - 2578C/A [rs699947], -460T/C [rs833061, +405C/ G [rs2010963], and + 936C/T [rs3025039]) and the risk of renal cell carcinoma are ambiguous and controversial. The aim of this investigation was to investigate this relationship in a series of Caucasian Spanish patients. MATERIALS AND METHODS: A case-control study was performed with 216 cases and 280 controls, genotyping subjects for VEGF polymorphisms using the predesigned TaqMan single nucleotide polymorphism (SNP) genotyping assay (Applied Biosystems, Foster City, CA, USA). The combined effect of the four gene polymorphisms on overall survival was studied by haplotype analysis. RESULTS: The overall results suggest that polymorphisms or haplotypes in the VEGF gene do not modify the risk of RCC. We were unable to replicate the association of the -460T/C (rs833061) polymorphism with renal cancer risk. Data were also gathered on clinical-pathological results, tumor size, clinical stage, histological grade, and survival. Conclusions: According to our analysis of their contribution to prognostic factors, VEGF polymorphisms do not appear to exert a significant influence on RCC progression or prognosis. This finding might be explained by the tumor biology and pathogenesis of clear cell RCC. Additional studies with larger sample sizes are needed in different ethnic groups to further assess this association.

PMID: 23073296 [PubMed - as supplied by publisher]

Tag-single nucleotide polymorphism-based human leukocyte antigen genotyping in celiac disease patients from northeastern Italy.

Hum Immunol. 2011 Apr 8;

Authors: Vatta S, Fabris A, Segat L, Not T, Crovella S

We genotyped celiac disease (CD)-associated haplotypes DQ2.5, DQ8, DQ2.2, and DQ7 in 1005 CD patients from North Eastern Italy using a Tag-single nucleotide polymorphism (SNPs) approach and real time PCR platform, checking the accuracy and reliability of the method and comparing it to traditional PCR-SSP. Only 14 of 2010 chromosomes analyzed (0.7%) showed discrepancies between the Tag-SNPs real-time polymerase chain reaction (PCR) method and the PCR-single-strand polymorphism (SSP) technique, indicating a high sensitivity and specificity (ranging from 0.987 to 1 and from 0.998 to 0.999, respectively) for tagging with respect to corresponding human leukocyte antigen (HLA) alleles identified by PCR-SSP. Moreover, the overall cost of the Tag-SNPs HLA typing method was low (3 to 4 €/sample instead of 35 to 70 €/sample with commercial kits), making it suitable for mass screenings. Hence, we believe that the Tag-SNPs HLA typing could be used to complement or replace classic HLA typing in at high-risk groups, for research purposes and eventually in population screening programs.

PMID: 21513759 [PubMed - as supplied by publisher]

HLA class II typing in newborns reveals a low frequency of the DRB1*04 allele and a high frequency of DRB1*11 allele in three regions of continental Italy.

Hum Immunol. 2004 Apr;65(4):366-72

Authors: Galgani A, Petrone A, Spoletini M, Hodge A, Del Buono ML, Locatelli M, Buzzetti R,

As part of a longitudinal study aimed at defining the natural history of prediabetic autoimmunity and predicting the risk of future cases of type 1 diabetes, 3607 newborns from three regions of continental Italy (Lombardia, Liguria, and Lazio) were subjected to genetic testing to determine human leukocyte antigen-DRB1 (HLA-DRB1) and -DQB1 allele and phenotype frequencies. Polymerase chain reaction and immobilized sequence-specific oligonucleotide probe assays were used to identify ten DRB1 allele lineages and three DQB1 alleles. No major inter-regional differences emerged in the allelic distribution indicating homogeneous distribution of the HLA DRB1-DQB1 alleles among the three regions analyzed. Comparison of our data with those published for other Caucasian populations reveals that these three regions are characterized by a very low frequency of DRB1*04 (8%) and a high frequency of DRB1*11 (25%). The phenotype frequencies of HLA-DQB1*0302 and DQB1*0602 observed are also lower than those reported for other populations. Furthermore, the DRB1*04-DQB1*0302 haplotype was relatively infrequent in our population (5.3% of the newborns tested). These findings furnish a genetic "portrait" of the populations of the analyzed regions that will be useful not only for investigation of the genetic risk of type 1 diabetes mellitus in Italy but also for studies of other autoimmune diseases related to HLA genotypes.

PMID: 15120192 [PubMed - indexed for MEDLINE]

The rare HLA-DQA1*03-DQB1*02 haplotype confers susceptibility to type 1 diabetes in whites and is preferentially associated with early clinical disease onset in male subjects.

Hum Immunol. 2004 Jul;65(7):729-36

Authors: van Autreve JE, Weets I, Gulbis B, Vertongen F, Gorus FK, van der Auwera BJ,

The heterozygous combination of DQA1*03-DQB1*0302 (DQ8) and DQA1*05-DQB1*0201 (DQ2) confers the highest known HLA-DQ-linked risk for type 1 diabetes, suggesting a role for transcomplementation. The trans-heterodimer encoded by DQA1*03 and DQB1*02 is also rarely observed in cis in whites. Islet antibody-positive diabetic patients (P; n = 2,238) and control subjects (C; n = 2,223) of white descent were genotyped by a HLA-DQA1-DQB1 dot-blot method. The presence of the DQA1*03-DQB1*02 haplotype was observed in 22 patients (1%) versus 6 controls (0.3%) (odds ratio [OR] = 3.7, p = 0.005). It was more prevalent in whites of Northern African descent, but both in European (n = 3,813) and in Northern African whites (n = 648), the DQA1*03-DQB1*02 haplotype tended to be associated with diabetes (respectively, P 0.3% vs. C 0.03%, OR = 12.2, p = 0.005; and P 2.1% vs. C 0.6%, OR = 3.8, p = 0.03). DRB1 typing revealed that DQA1*03-DQB1*02 is usually associated with the DRB1*0405 risk allele in European patients and with DRB1*0405, DRB1*07 and DRB1*09 in Northern African whites. Like in DQ2/DQ8-positive patients, the presence of DQA1*03-DQB1*02 is preferentially associated with younger age at clinical onset than in other genotypes, but unlike in subjects carrying DQ2/DQ8, earlier clinical manifestation was mostly restricted to male subjects, often carrying DR3 and/or DQB1*02 on the other chromosome. These results are compatible with an effect of cis-encoded heterodimers or with previously suggested interactions of X-linked genetic factors with (DR3-)DQB1*02 haplotypes.

PMID: 15301863 [PubMed - indexed for MEDLINE]