GJA4/Connexin 37 Mutations Correlate with Secondary Lymphedema Following Surgery in Breast Cancer Patients.

Lymphedema is a condition resulting from mutations in various genes essential for lymphatic development and function, which leads to obstruction of the lymphatic system. Secondary lymphedema is a progressive and incurable condition, most often manifesting after surgery for breast cancer. Although its causation appears complex, various lines of evidence indicate that genetic predisposition may play a role. Previous studies show that mutations in connexin 47 are associated with secondary lymphedema. We have tested the hypothesis that connexin 37 gene mutations in humans are associated with secondary lymphedema following breast cancer surgery. A total of 2211 breast cancer patients were screened and tested for reference single nucleotide polymorphisms (SNPs) of the GJA4 gene (gap junction protein alpha 4 gene). The results presented in this paper indicate that two SNPs in the 3' UTR (the three prime untranslated region) of the GJA4 gene are associated with an increased risk of secondary lymphedema in patients undergoing breast cancer treatment. Our results provide evidence of a novel genetic biomarker for assessing the predisposition to secondary lymphedema in human breast cancer patients. Testing for the condition-associated alleles described here could assist and inform treatment and post-operative care plans of breast cancer patients, with potentially positive outcomes for the management of disease progression.

Association of CLU and TLR2 gene polymorphisms with late-onset Alzheimer disease in a northwestern Iranian population.

BACKGROUND/AIM: A number of genetic variants from different genes have been reported to be related to late-onset Alzheimer disease (LOAD) susceptibility. From these genes, polymorphisms in CLU and TLR2 have been replicated in several studies. In this study we examined the association of rs11136000 in CLU and the TLR2 -196 to -174 del polymorphism with the risk of LOAD in a northwestern Iranian population. MATERIALS AND METHODS: We conducted a case-control study with a dataset of 160 LOAD patients and 163 healthy controls. To examine polymorphisms of CLU and TLR2 in LOAD we used the PCR/RFLP method and genotype frequencies were statistically determined. RESULTS: There was no association between CLU polymorphism and the risk of LOAD, but for deletion in TLR2 we found significant differences between LOAD and the control group (P > 0.001, OR = 0.55). CONCLUSION: This result suggests that the TLR2 -196 to -174 del polymorphism is an additional risk factor for LOAD. Allelic frequencies of CLU may have no effect on risk of LOAD.