HER2Ile655Val Polymorphism and Risk of Breast Cancer

HER2 plays a vital role in the development and progression of several types of human cancer, so the HER2 becomes one of major targets for HER2-positive breast cancer treatment. Several reports have shown that the HER2 oncogene expression relates to clinicopathological factors in cancer patients. HER2Ile655Val single nucleotide polymorphism associates with malignant tumors, including prostate cancer, colorectal cancer, osteosarcoma, gastric cancer, uterine cervical carcinoma, fibroadenoma, and breast cancer. To understand the precise association, this chapter was described to estimate the association between HER2Ile655Val single nucleotide polymorphism and susceptibility to breast cancer. Our findings suggest that the Val allele in HER2 codon 655 single nucleotide polymorphism is strongly associated with the risk of breast cancer. HER2Ile655Val single nucleotide polymorphism might also be a susceptibility factor that favors early-onset breast cancer.

Copper Imbalance in Alzheimer’s Disease: Meta-Analysis of Serum, Plasma, and Brain Specimens, and Replication Study Evaluating ATP7B Gene Variants

Evidence indicates that patients with Alzheimer’s dementia (AD) show signs of copper (Cu) dyshomeostasis. This study aimed at evaluating the potential of Cu dysregulation as an AD susceptibility factor. We performed a meta-analysis of 56 studies investigating Cu biomarkers in brain specimens (pooled total of 182 AD and 166 healthy controls, HC) and in serum/plasma (pooled total of 2929 AD and 3547 HC). We also completed a replication study of serum Cu biomarkers in 97 AD patients and 70 HC screened for rs732774 and rs1061472 ATP7B, the gene encoding for the Cu transporter ATPase7B. Our meta-analysis showed decreased Cu in AD brain specimens, increased Cu and nonbound ceruloplasmin (Non-Cp) Cu in serum/plasma samples, and unchanged ceruloplasmin. Serum/plasma Cu excess was associated with a three to fourfold increase in the risk of having AD. Our replication study confirmed meta-analysis results and showed that carriers of the ATP7B AG haplotype were significantly more frequent in the AD group. Overall, our study shows that AD patients fail to maintain a Cu metabolic balance and reveals the presence of a percentage of AD patients carrying ATP7B AG haplotype and presenting Non-Cp Cu excess, which suggest that a subset of AD subjects is prone to Cu imbalance. This AD subtype can be the target of precision medicine-based strategies tackling Cu dysregulation.

TaaI/Cdx-2 AA Variant of VDR Defines the Response to Phototherapy amongst Patients with Psoriasis

1,25-dihydroxyvitamin-D3 plays a central role in the immune system via binding to the vitamin D receptor. VDR polymorphisms have been associated with multiple autoimmune disorders, including psoriasis. Until now, five VDR polymorphisms, FokI, ApaI, BsmI, TaqI and TaaI/Cdx2, have been studied in psoriasis, with contradicting results. Therefore, this study aimed to evaluate the association of VDR polymorphisms with susceptibility to psoriasis, effectiveness of NB-UVB phototherapy and concentration of proinflammatory cytokines and vitamin D amongst the Polish population. VDR polymorphisms were analyzed by PCR-RFLP or real-time PCR. We found that the frequency of the TaaI/Cdx-2 GG genotype was significantly higher in psoriasis patients and was associated with regulation of IL-17 and IL-23 concentration. Moreover, TaaI/Cdx-2 AA might have a significant effect on the response to phototherapy amongst patients with psoriasis. Our results suggest that VDR is a susceptibility factor for psoriasis development. Moreover, TaaI/Cdx-2 variants have a significant effect on the response to phototherapy amongst patients with psoriasis and regulation of inflammatory response via decrease of IL-17 and IL-23 level after UVB phototherapy in the Polish population. Results of our study provide some evidence in support of the hypothesis that the vitamin D signaling pathway may be of relevance for pathogenesis and treatment of psoriasis.

APOA1 (-75 G>A and 83 C>T) and APOB (2488 C>T) polymorphisms and its association with Myocardial Infarction, lipids and apolipoproteins in patients with Type 2 Diabetes Mellitus

IntroductionThe increased risk of myocardial infarction (MI) in T2DM is well documented. Polymorphisms in APOA1 and APOB genes allow us to identify new genetic markers in Mexican population with T2DM and MI.Material and methodsWe studied 135 patients with DMT2 and MI (DI); another 85 non-infarcted diabetic individuals with DMT2 but without previous ischemic events (NID) and 242 Healthy subjects (HS), all three groups were selected with the aim to investigate the association between the polymorphisms and infarction when T2DM is present or absent.Results-75 G>A polymorphism: differences were found in genotype distribution between DI and NID individuals (OR: 2.01, CI:1.117-3.623, p= 0.019) with an increased risk for A in the dominant model (OR: 1.77, CI: 1.020-3.084, p= 0.042); also concentrations of ApoA-I for A/A were lower in comparison with G/A (p = 0.038) and LDL-C and HDL-C levels were lower in G/A respecting to G/G carriers. 83 C> T polymorphism of APOA1: for DI individuals: HDL-C was lower in T/T respecting to C/C and triglyceride levels were lower in C/T respect to C/C carriers.ConclusionsThe -75 G>A APOA1 polymorphism could be considered as a susceptibility factor for Myocardial Infarction in individuals with T2DM and 2488 C>T APOB polymorphism is associated with changes in HDL-C and LDL-C and triglycerides in the same group.roup.