Receptor Gene Polymorphisms In Patients Research Articles

Estrogen receptor gene polymorphisms in patients with idiopathic premature ovarian failure

It has been reported that polymorphisms in the estrogen receptor (ER)-alpha gene (ESR1) may be associated with reproductive patterns of women. This study was performed to investigate whether the genetic polymorphisms of the ER-alpha gene are associated with idiopathic premature ovarian failure (POF) in a Korean population. The subjects were 126 idiopathic POF patients and 221 post-menopausal controls recruited from university hospitals between 1999 and 2004. Genotyping was performed by MGB primer/probe Taqman assay. Haplotypes were deduced by using the Haploview version 4.1. Bonferroni correction was applied for the correction of multiple testing. There was no significant difference in the allele distribution of the ER-alpha gene (TA)n repeats between the POF and the control group. For the PvuII polymorphism, the POF group showed a higher frequency of TT genotype compared with the controls (41.3 versus 26.3%, P = 0.004, 98.75% CI 1.8-28.2%). No significant difference was found in the distribution of the XbaI polymorphism between the POF and the control group. Haplotype analysis showed that the frequency of TA haplotype was significantly higher in the POF patients compared with the controls (64.7 versus 52.7%, P = 0.002, 98.75% CI 2.4-21.6%). These findings suggest that the ER-alpha gene polymorphisms may be associated with idiopathic POF.

Killer cell immunoglobulin-like receptor gene polymorphisms in patients with leukemia: Possible association with susceptibility to the disease

Accumulating evidences suggest that killer cell immunoglobulin-like receptors (KIRs) contribute to the pathogenesis of diverse kinds of diseases. However, the functions and effects of KIR gene polymorphisms in the development of diseases remain largely unknown, especially about the activating KIR genes. To investigate the association of KIR gene polymorphisms with subtypes of leukemia, we carried out the present study on 263 patients with leukemia and 239 healthy controls by means of polymerase chain reaction-sequence-specific primer and analysis, and then all data were analyzed by Logistic regression method. Our results showed that the frame genotypes of KIR2DL4, 3DL2, 3DL3 and 3DP1 were expressed in all patients and all controls. The genotypes of KIR2DL1, 2DL3, 3DL1, and 2DP1 were most prevalent genotypes whose rates were more than 95% in all patients and all controls. The rate of activating KIR2DS4 was much higher in patients with CML than that in healthy controls ( P < 0.001) while the activating KIR2DS3 was lower in patients with ALL compared with healthy controls ( P < 0.05). There was no significant change of KIR genes found in patients with NALL. In conclusion, this study suggests that the activating KIR2DS4 may serve as CML susceptive gene to trigger leukemia development, while KIR2DS3 is possibly a protect gene of ALL.

UP.25: Do Androgen Receptor Polymorphisms Contribute to an Increased Risk for Benign Prostate Hyperlasia (BPH)?

Prostate development requires the presence of testicular androgens. The androgen receptor (AR) gene may play important role in this process and has variable length of CAG repeats. To evaluate possible involvement of the androgen receptor in susceptibility to BPH, we examined androgen receptor gene polymorphisms in patients with well documented BPH compared to controls.

Viral Vector–mediated Delivery of Estrogen Receptor-α to the Hippocampus Improves Spatial Learning in Estrogen Receptor-α Knockout Mice

Estrogen, which influences both classical genomic and rapid membrane-associated signaling cascades, has been implicated in the regulation of hippocampal function, including spatial learning. Gene mutation studies suggest that estrogen effects are mediated by estrogen receptor-α (ER-α); however, because gonadal steroids influence the organization of the hippocampus during development, it has been difficult to distinguish developmental effects from those specific to adults. In this study we show that lentiviral delivery of the gene encoding ER-α to the hippocampus of adult ER-α-knockout (ER-αKO) mice restores hippocampal responsiveness to estrogen and rescues spatial learning. We propose that constitutive estrogen receptor activity is important for maintaining hippocampus-dependent memory function in adults.

Relation between P-wave dispersion and angiotensin II type 1 receptor gene polymorphisms in patients with a first anterior acute myocardial infarction

Relation between P-wave dispersion and angiotensin II type 1 receptor gene polymorphisms in patients with a first anterior acute myocardial infarction

Neuropsychiatric Inventory Workshop: Behavioral and Psychologic Symptoms of Dementia in Asia

The Neuropsychiatric Inventory (NPI) was introduced in 1994 and has since become a standard instrument for clinical trials and other types of behavioral research in dementing disorders. Its reliability and validity have been confirmed. The NPI was the subject of a workshop in Asia in conjunction with the International Workgroup on Dementia Drug Guidelines (IWG). Investigators using the NPI from 4 Asian areas--Taiwan, Hong Kong, Japan, Thailand--presented conclusions from their research. A high prevalence of behavioral disturbances across Asian countries was found and the rates are similar to those observed in Western countries. Apathy is more difficult to detect and characterize in Asian populations. Neurobiologic studies show an excess of some serotonin receptor gene polymorphisms in patients without behavioral disturbances and positron emission tomography reveals reductions in frontal lobe metabolism in patients manifesting depression as measured by the NPI. Studies in Thailand show relationships among verbal fluency, activities of daily living, and neuropsychiatric symptoms particularly agitation, apathy, and disinhibition. This suggests a triad of symptoms of behavioral abnormalities, executive dysfunction, and abnormalities of activities of daily living that impugn frontal lobe function. The NPI is a reliable and useful instrument to characterize behavioral changes in Asian and Western populations.

Vitamin D receptor gene polymorphisms in patients with urolithiasis

Urolithiasis is a multifactorial disease, the onset and severity of which is influenced by both genetic and environmental factors. This study represents an investigation of the role of vitamin D receptor (VDR) gene polymorphisms (ApaI, BsmI, and TaqI) and combined genotypes in urolithiasis in a Turkish population. We studied 110 patients with urinary stones and 150 control subjects. The polymorphic regions were amplified using polymerase chain reaction, followed by digestion with restriction enzymes BsmI, ApaI, and TaqI, and analyzed electrophoretically. Genotype and allele frequencies were calculated, and the association with urolithiasis, family history, and recurrence of stone was investigated. Our data provide no evidence for an association between urolithiasis and VDR ApaI, BsmI, and TaqI genotypes. We also analyzed the effects of VDR ApaI, BsmI, and TaqI genotypes in combination; the "GTT" VDR haplotype, constructed from three adjacent restriction fragment length polymorphisms was overrepresented among the urolithiasis patients. However, no significant differences between heterozygous carriers (OR 1.302; 95% CI 0.527-3.215) and homozygous carriers (OR 3.39; 95% CI 0.719-15.985) were observed in our study population. A significant association was found only between the ApaI polymorphism and family history (P=0.017; chi (2)=5.657). Our data indicate that the VDR ApaI, BsmI, and TaqI polymorphisms do not confer a significant risk for urolithiasis.

Left Ventricular Size, Mass and Function in Relation to Angiotensin-Converting Enzyme Gene and Angiotensin-II Type 1 Receptor Gene Polymorphisms in Patients with Coronary Artery Disease

The objective of the present study was to analyse the potential synergistic influence of the insertion/deletion polymorphism of the angiotensin-converting enzyme gene (I/D ACE) and the A1166C polymorphism of the angiotensin-II type 1 receptor gene polymorphisms (A1166C AT1R) on the left ventricular size and performance. Three hundred sixty and one consecutive, Caucasian patients with angiographically confirmed coronary artery disease (CAD) were enrolled into the study. Left ventricular diameter, mass and function were evaluated by echocardiography. Screening for the I/D ACE and A1166C AT1R genotypes was performed by polymerase chain reaction of genomic DNA, followed by restriction enzyme digestion and agarose gel electrophoresis. The I/D ACE and A1166C AT1R genotypes separately were not significantly associated with the left ventricular size and function parameters in CAD patients. However, trends towards decreased left ventricular ejection fraction (LVEF) as well as increased left ventricular end-diastolic diameter (LVEDD) and left ventricular mass index (LVMI) were observed when patients with genotype DD+CC/AC and DD+CC were compared to patients homozygous only in one locus (DD or CC). Significant increase in LVEDD and LVMI was observed only in patients with a history of anterior myocardial infarction with combined genotype DD+CC/AC or DD+CC. This study does not support the role of the ACE I/D and AT1R A1166C polymorphisms in the determination of the left ventricular size and performance in patients with significant coronary atherosclerosis. However, it indicates that the influence of polymorphisms may be present in specific patient populations.

ACE and angiotensin II and nonarteritic anterior ischemic optic neuropathy: Author reply

Dr. Donahue’s letter expresses concerns that in our article, “The Role of Angiotensin Converting Enzyme and Angiotensin II Type 1 Receptor Gene Polymorphisms in Patients with Nonarteritic Anterior Ischemic Optic Neuropathy (NAION),” further statistical analysis are required to support our conclusion that angiotensin-converting enzyme (ACE) and angiotensin II type 1 receptor (AT1R) have no role in the pathogenesis of the disease. The insignificant P values in our study could result from true lack of effect or from small sample sizes and, consequently, low power. We have carried out the power calculations requested by Dr. Donahue with respect to a 20% absolute difference in the allele frequencies of the presumed risks (D allele in the case of ACE and C allele in the case of AT1R). The calculations were based on the use of a two-sided 5% test. The power to detect a 20% difference in ACE and AT1R was 98.7% and 95.2%, respectively. More cogent is a computation of the 95% confidence intervals (CI) for the differences in the D and C allele frequencies (NAION patients minus controls). The 95% CI for the D allele of ACE was −14.9, 6.5 and for the C allele of AT1R, was −3.3, 16.4. For both polymorphisms, the 95% CI indicated small differences; and it ruled out a 20% increment among NAION patients over the controls. Thus, additional calculations support our conclusion that ACE and AT1R polymorphisms have no role in the pathogenesis of NAION.