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At least 415 records · Page 23Linked to original sources
PubMed2005

Impact of gene polymorphisms on clinical outcome for stage IV melanoma patients treated with biochemotherapy: an exploratory study.

PURPOSE: Biochemotherapy can achieve high response rates in advanced melanoma, but the factors that influence regression and survival remain unknown. The present exploratory study tested the hypothesis that cytokine gene polymorphisms predict clinical outcome in stage IV melanoma patients treated with biochemotherapy. EXPERIMENTAL DESIGN: Ninety patients with stage IV melanoma were treated with biochemotherapy, including cisplatin, vinblastine, and dacarbazine combined with interleukin (IL)-2 and IFN-alpha either with or without tamoxifen. Cytokine gene polymorphisms for IFN-gamma (+874A-->T) and IL-10 (-1082G-->A) were assessed. X-ray repair cross-complementing gene 1 (XRCC1; Arg399Gln), xeroderma pigmentosum complementary group D (XPD; Lys751Gln), and excision repair cross-complementing gene 1 (ERCC1; codon 118) DNA repair polymorphisms were also determined. RESULTS: IFN-gamma (+874A-->T) gene polymorphism was statistically significantly associated with response (P = 0.001), progression-free survival (P = 0.0012), and overall survival (P < 0.001), whereas the IL-10 polymorphism was marginally associated with response (P = 0.03) and overall survival (P = 0.065). Multivariate analysis revealed that IFN-gamma (+874A-->T) independently predicted overall survival (P = 0.003). The ERCC1 polymorphism was weakly associated with overall survival (P = 0.045). Combining polymorphisms for IFN-gamma, IL-10, and ERCC1 stratified patients into four distinct groups with significantly different clinical outcome (P < 0.001), so that patients with more "favorable" polymorphisms had a better outcome. CONCLUSIONS: Cytokine gene polymorphisms predicted clinical outcome for advanced melanoma patients who received biochemotherapy. The combined effects of multiple genetic polymorphisms may provide more accurate prognostic information. Additional independent studies are needed to confirm these pilot findings.

Adolescent↗
PubMed2004

Angiotensin-I converting enzyme gene polymorphism in Turkish type 2 diabetic patients.

Non-insulin dependent diabetes mellitus is often associated with some complications such as nephropathy, retinopathy and neuropathy. Genes of the renin angiotensin system are potential candidate genes for diabetic complications. We investigated the relationship between angiotensin converting enzyme (ACE) gene polymorphism in type 2 diabetic patients with and without diabetic nephropathy. Seventy five patients (25 type 2 diabetic patients with nephropathy, 50 type 2 diabetic patients without nephropathy) and 37 healthy controls were studied. Gene polymorphism of ACE was determined by PCR (polymerase chain reaction) amplification using allele-spesific primers. The frequencies of ACE DD, ID and II genoypes among the patients with type 2 diabetic patients were found 48%, 42%, 10% whereas in control subjects, 27%, 60%, 13% respectively. Type 2 diabetic patients carrying DD genotype without nephropathy increased 1.77 fold than control subjects (P < 0.05). There is no significant correlation between diabetic nephropathy and ACE gene polymorphism. But we found that ACE DD genotype increased significantly in type 2 diabetic patients compared to control subjects (P <.05).

Adult↗
PubMed2004

Analysis of MHC genes in a Tunisian isolate with autoimmune thyroid diseases: implication of TNF -308 gene polymorphism.

Autoimmune thyroid diseases (AITDs), which include Hashimoto thyroiditis (HT), Graves' disease (GD) and primary idiopathic myxoedema (PIM), are recognized as multifactorial diseases. In this study, we have examined single and haplotypic genetic variation across the major histocompatibility complex (MHC) in a Tunisian isolate with a high prevalence of AITDs (62 patients: 32 with GD, 9 with HT and 21 with PIM). Genotyping was performed for HLA class I and II alleles as well as polymorphisms within tumor necrosis factor (TNF), lymphotoxin alpha (TLalpha) and heat shock protein (HSP70-02 and HSP70-hom) genes. Our results showed association of HLA-A2-B50-TNF 2 haplotype with AITDs (p = 0.045). Linkage analysis using Simwalk2 program has shown significant result with TNF -308 gene polymorphism (p = 0.03). The FBAT has given evidence for genetic association with TNF -308 and HLA-DR gene polymorphisms. TNF 2 allele was associated with GD (p = 0.0011), whereas TNF 1, HLA-DR11 and DR12 (p = 0.0039, p = 0.00089 and p = 0.0056, respectively) were rather implicated in HT pathogenesis. Results found by TDT-STDT have confirmed the involvement of the TNF -308 gene polymorphism in AITD pathogenesis (p < 10(-9)).

Adolescent↗
PubMed2006

Angiotensin converting enzyme gene polymorphisms do not predict the course of idiopathic nephrotic syndrome in Swiss children.

AIM: Contradictory reports exist about a correlation of angiotensin I converting enzyme (ACE) gene polymorphisms to the outcome of idiopathic nephrotic syndrome (INS) in children. We investigated the frequency of ACE polymorphisms and their impact on the clinical course of INS in children in a Swiss hospital. METHODS: The ACE gene polymorphism (I, insertion; D, deletion) was assessed in 32 children - 22 with steroid-sensitive INS and 10 with steroid-resistant INS - with a median age at onset of INS of 2.9 years (range 1.1-15.0). Polymerase chain reaction amplification was performed on genomic DNA isolated from blood leucocytes. Results were correlated to clinical course and renal morphology. RESULTS: The ACE genotype was I/I, I/D and D/D in two, 12 and eight patients, respectively, with steroid-sensitive INS, and in one, eight and one patient, respectively, with steroid resistance. Renal morphology, available in 25 patients showed minimal change glomerulopathy in 17 patients (14 steroid-sensitive; three steroid-resistant) and focal segmental glomerulosclerosis in eight (one steroid-sensitive; seven steroid-resistant). There was no significant correlation between ACE genotype and steroid responsiveness, histology or outcome. ACE genotype was I/I, I/D and D/D in none, 12 and five patients, respectively, with minimal change glomerulopathy, and in one, five and two patients, respectively, with focal segmental glomerulosclerosis. Six patients with steroid-resistant nephrotic syndrome went into end stage renal disease; ACE genotype was I/I in one and I/D in five, but none were D/D. CONCLUSION: In contrast to previous reports, ACE gene polymorphism is irrelevant for clinical outcome, steroid responsiveness or morphology in Swiss children with INS.

Age of Onset↗
PubMed2004

Relation between XbA1 apolipoprotein B gene polymorphism and cardiovascular risk in a type 2 diabetic cohort.

AIM: To evaluate in a prospective study the association of XbA1 apolipoprotein B (apoB) gene polymorphism with lipid parameters and cardiovascular (CV) events in a type 2 diabetic cohort. METHODS AND RESULTS: A cohort of 212 type 2 diabetic patients, free of any cardiovascular complication, was studied. Cardiovascular events were registered for all the patients for 5 years. XbA1 apolipoprotein B gene polymorphism was analysed by PCR-RFLP method. A mild increase in HbA1c was found in X+X+ carriers (P = 0.014). Despite this lower glycemic control, there were no differences between genotype subgroups for lipid parameters except for apoB, significantly higher in X+X+ than in X-X- subjects. In univariate analysis, the cardiovascular events rate was higher in X-X- but did not reach statistical significance (P =0.07). In stepwise multivariate regression analysis, cardiovascular events risk was significantly higher in X- carriers (P = 0.014) and also in smokers, microalbuminuric and older patients. CONCLUSIONS: We report for the first time in a prospective study the association of XbA1 apolipoprotein B gene polymorphism and cardiovascular events in a diabetic population. The mechanism underlying the excess of cardiovascular risk in X- carriers, despite a better metabolic profile, is likely to involve a linkage disequilibrium between apolipoprotein B gene locus and another gene locus related to cardiovascular risk.

Apolipoproteins B↗
PubMed2003

Angiotensin-converting enzyme polymorphism gene and evolution of nephropathy to end-stage renal disease.

Genetic polymorphisms of the renin-angiotensin system (RAS) have been implicated in the pathogenesis of nephropathy and end-stage renal disease (ESRD). The association between angiotensin-converting enzyme (ACE) gene polymorphism and nephropathy evolution was studied. A random sample of 161 subjects from the Nephrology Department (of Hospital de Sant Pau) were divided into two groups: (i) 117 with end-stage renal disease; (ii) 44 with established nephropathy; and (iii) control groups of 129 subjects. The ACE gene polymorphism was performed by using polymerase chain reaction. High DD genotype presentation was observed in the two groups of subjects with nephropathy (46.12 and 61.37%, respectively vs 35.66% in controls; P < 0.0482), and also, a decrease was observed in the II genotype (6.4 and 4.54%, respectively vs 13.17% in controls, P < 0.0404). Glomerular filtration rate (GFR) was evaluated after 44 months of follow up. An important decrease of GFR was observed in patients with DD polymorphism versus other genotypes (initial, 32.3 +/- 7.9 and at 44 months, 18.35 +/- 3.3 mL/min vs 31.4 +/- 11.9 and 11.7 +/- 3.2 mL/min; P < 0.039). In a non-longitudinal study of patients in ESRD, patients with an ACE-DD genotype had a lower period of time between diagnosis of nephropathy and ESRD than patients with other genotypes (10.45 +/- 9.32 vs 19.5 +/- 8.4 years; P < 0.034). In conclusion, the ACE gene that controls RAS response may influence the development and progression of nephropathy to ESRD. Patients who develop several types of nephropathy have a higher risk of severe evolution if they have a profile of ACE-DD genotype.

Disease Progression↗
PubMed2004

Vitamin D receptor gene polymorphisms in relation to Vitamin D related disease states.

The role in skeletal metabolism of the steroid hormone Vitamin D and its nuclear receptor (VDR) is well known. In addition, however, Vitamin D is also involved in a wide variety of other biological processes including modulation of the immune response and regulation of cell proliferation and differentiation. Variations in the Vitamin D endocrine system have thus been linked to several diseases, including osteoarthritis, diabetes, cancer, cardiovascular disease and tuberculosis. Evidence to support this pleiotropic character of Vitamin D has included epidemiological studies on circulating Vitamin D hormone levels, but also genetic epidemiological studies. Genetic studies provide excellent opportunities to link molecular insights with epidemiological data and have therefore gained much interest. DNA sequence variations which occur frequently in the population are referred to as "polymorphisms" and are usually suspected of having only modest and subtle effects. Recent studies have indicated many polymorphisms to exist in the VDR gene, but the influence of VDR gene polymorphisms on VDR protein function are largely unknown. Sofar, three adjacent restriction fragment length polymorphisms (RFLP) for BsmI, ApaI and TaqI, respectively, at the 3' end of the VDR gene have been the most frequently studied sofar. But because these polymorphisms are probably non-functional, linkage disequilibrium (LD) with one or more truly functional polymorphisms elsewhere in the VDR gene is assumed to explain the associations observed. Research is therefore focussed on documenting additional polymorphisms across the VDR gene to verify this hypothesis, and on trying to understand the functional consequences of the variations. Substantial progress has been made including the discovery of novel polymorphisms in the large promoter region of the VDR gene. Eventually, results of this research will deepen our understanding of variability in the Vitamin D endocrine system and might find applications in risk-assessment of disease and in predicting response-to-treatment.

Humans↗
PubMed1998

Impact of the MHC-encoded HLA-DMA, DMB, and LMP2 gene polymorphisms on kidney graft outcome.

We previously studied the relationship between TAP1 and TAP2 gene polymorphism and compatibility in kidney graft outcome and reported that the currently described TAP1 and TAP2 gene polymorphisms did not influence the incidence of acute rejection episodes. In this study, we report on the effect of polymorphism and matching of HLA-DMA, -DMB, and LMP2 genes on kidney graft outcome. This study was performed on 102 selected kidney recipients who experienced two or more acute rejection episodes (rejection group) during follow up and who were compared to a group of 150 patients who never had rejection (non rejection group). Although a significant effect of HLA-DR matching was observed between these two groups, our data suggest that matching for all the new genes located in the HLA class II region (TAP1, TAP2, LMP2, HLA-DMA and -DMB) does not influence the kidney graft outcome. However, a significant increase (pc < 0.05) of DMA*0102 allele was observed in the recipients of the rejection group as compared to those of the non rejection group. This effect was not due to a linkage disequilibrium between DMA and HLA-DR loci and suggests that this specific HLA-DMA allele could play a role in the indirect pathway of class II presentation of donor antigens.

Adult↗
PubMed2005

Predicting drug response and toxicity based on gene polymorphisms.

The sequencing of the human genome has allowed the identification of thousands of gene polymorphisms, most often single nucleotide polymorphims (SNP), which may play an important role in the expression level and activity of the corresponding proteins. When these polymorphisms occur at the level of drug metabolising enzymes or transporters, the disposition of the drug may be altered and, consequently, its efficacy may be compromised or its toxicity enhanced. Polymorphisms can also occur at the level of proteins directly involved in drug action, either when the protein is the target of the drug or when the protein is involved in the repair of drug-induced lesions. There again, these polymorphisms may lead to alterations in drug efficacy and/or toxicity. The identification of functional polymorphisms in patients undergoing chemotherapy may help the clinician prescribe the optimal drug combination or schedule and predict with more accuracy the response to these prescriptions. We have recorded in this review the polymorphisms that have been identified up till now in genes involved in anticancer drug activity. Some of them appear especially important in predicting drug toxicity and should be determined in routine before drug administration; this is the case of the most common variations of thiopurine methyltransferase for 6-mercaptopurine and of dihydropyrimidine dehydrogenase for fluorouracil. Other appear determinant for drug response, such as the common SNPs found in glutathione S-transferase P1 or xereoderma pigmentosum group D enzyme for the activity of oxaliplatin. However, confusion factors may exist between the role of gene polymorphisms in cancer risk or overall prognosis and their role in drug response.

Cytochrome P-450 Enzyme System↗
PubMed2005

Effect of gene polymorphisms on lipoprotein levels in patients with dyslipidemia of metabolic syndrome.

Dyslipidemia in the metabolic syndrome (MS) is considered to be one of the most important risk factors for atherosclerosis. It is characterized by hypertriglyceridemia, low concentration of plasma HDL-cholesterol, predominance of small dense LDL particles and an increased concentration of plasma apolipoprotein B (apoB). The pathogenesis of this type of dyslipidemia is partially explained, but its genetic background is still unknown. To evaluate the influence of cholesterol ester transfer protein (CETP) TaqIB polymorphism, lipoprotein lipase (LPL) PvuII and HindIII polymorphisms, hepatic lipase (LIPC) G-250A polymorphism and apolipoprotein C-III (APOC3) SstI gene polymorphism on lipid levels in dyslipidemia of the metabolic syndrome, 150 patients with dyslipidemia of metabolic syndrome were included. 96 % of patients had type 2 diabetes. The patients did not take any lipid lowering treatment. The exclusion criterion was the presence of any disease that could affect lipid levels, such as thyroid disorder, liver disease, proteinuria or renal failure. Gene polymorphisms were determined using the polymerase chain reaction and restriction fragment length polymorphisms. The genotype subgroups of patients divided according to examined polymorphisms did not differ in plasma lipid levels with the exception of apoB. The apoB level was significantly higher in patients with S1S1 genotype of APOC3 SstI polymorphism when compared with S1S2 group (1.10+/-0.26 vs. 0.98+/-0.21 g/l, p=0.02). Similarly, patients with H-H- genotype of LPL HindIII polymorphism had significantly higher mean apoB, compared with H+H- and H+H+ group (1.35+/-0.30 vs. 1.10+/-0.26 g/l, p=0.02). In the multiple stepwise linear regression analysis, apoB level seemed to be influenced by APOC3 SstI genotype, which explained 6 % of its variance. The present study has shown that the S1 allele of APOC3 SstI polymorphism and the H- allele of LPL HindIII polymorphism might have a small effect on apoB levels in the Central European Caucasian population with dyslipidemia of metabolic syndrome.

Aged↗
PubMed2004

Angiotensin-converting enzyme D/I gene polymorphism and age-related changes in pulse pressure in subjects with hypertension.

UNLABELLED: Background- Few studies have examined the possible influence of gene polymorphisms on the increase of systolic blood pressure (SBP) and pulse pressure (PP) with age, although in older populations, SBP>160 mm Hg or PP>60 mm Hg are strong mechanical factors predicting cardiovascular mortality. METHODS AND RESULTS: This cross-sectional study involved 315 men and 154 women with either systolic-diastolic or isolated systolic hypertension. Using polymerase chain reaction, the angiotensin-converting enzyme (ACE) D/I gene polymorphism was investigated separately in men and women, enabling us to determine the relationships between age and PP, SBP, and diastolic blood pressure (DBP) for each genotype in each population. In men, most of which were under 50 years of age, the slope of the age-PP and age-SBP (but not age-DBP) relationships differed significantly between genotypes (P=0.0096 and 0.0175). The interslope difference was unmodified after adjustments involving all of the following factors together: plasma glucose, cholesterol, creatinine, potassium, body weight, tobacco consumption, mean blood pressure, and previous antihypertensive therapy. Adjustment of the two latter parameters alone significantly attenuated the interslope difference. Based on logistic regressions, the DD genotype was shown to independently predict a PP>60 mm Hg but not a SBP>160 mm Hg. CONCLUSIONS: In men, the ACE D/I gene polymorphism independently modulates age-related increase of PP, and potentially modulates the resulting cardiovascular risk. This finding requires the development of long-term follow-up.

Adolescent↗
PubMed2005

[PPARdelta + 294T/C gene polymorphism related to plasma lipid, obesity and left ventricular hypertrophy in subjects with metabolic syndrome].

OBJECTIVE: To investigate the relationship between PPARdelta + 294T/C gene polymorphism and lipid profile, obesity and left ventricular hypertrophy (LVH) in patients with metabolic syndrome (MS). METHODS: This study was conducted in 300 patients with MS and 174 patients with essential hypertension (EH) and 143 patients with type 2 diabetes mellitus (T2DM). MS was diagnosed according to 1999 WHO criteria. Fasting insulin (FINS), fasting blood glucose (FBG), plasma lipids levels were measured, LVH was examined by Doppler echocardiography. The PPARdelta + 294T/C gene polymorphism were analyzed using polymerase chain reaction and subsequently digested by BSLI restriction endonuclease. RESULTS: The frequencies of the PPARdelta + 294T/C genotypes were not different among three groups. Compared with T2DM and EH, MS patients had significantly higher body mass index (BMI), plasma total cholesterol, TG and LDL-C levels (P < 0.01 or P < 0.05). LVM, LVMI and incidence rate of LVH were significantly higher in MS and EH patients than that in T2DM (P < 0.01). MS patients with CC genotype had significantly higher total cholesterol and LDL-C levels than those with TT and TC genotypes (total cholesterol in CC genotype: 6.13 +/- 1.86 mmol/L vs in TC genotype: 5.14 +/- 1.10 mmol/L, P < 0.05, and CC genotype: 6.13 +/- 1.86 mmol/L vs TT genotype: 4.99 +/- 1.42 mmol/L, P < 0.01; LDL-C in CC genotype: 3.82 +/- 1.52 mmol/L vs in TC genotype: 3.14 +/- 0.88 mmol/L, P < 0.05, and in CC genotype: 3.82 +/- 1.52 mmol/L vs in TT genotype: 2.90 +/- 0.87 mmol/L, P < 0.01). BMI and LVMI in MS patients with C allele carriers (CC + TC) were significantly higher than that of TT genotype (LVMI in CC + TC: 46 +/- 10 g/m(2.7) vs in TT: 44 +/- 10 g/m(2.7); BMI in CC + TC: 26 +/- 3 kg/m(2) vs in TT: 25 +/- 3 kg/m(2), P < 0.05). CONCLUSIONS: It is indicated that PPARdelta + 294T/C gene polymorphism in subjects with MS may be involved in the occurrence of obesity and dyslipidemia. MS patients with C allele had a predominant LVH than subjects with TT genotype.

Aged↗
PubMed2002

Gene polymorphisms, inflammatory diseases and cancer.

Genes whose products play a critical role in regulation of the immune response include the human leucocyte antigen (HLA) and cytokine families of genes. The HLA genes are the most polymorphic found in the human genome, and the bulk of this polymorphism results in functional differences in expressed HLA molecules, resulting in inter-individual differences in presentation of peptide antigens to T-cells. In addition, a considerable number of cytokine-associated gene polymorphisms have been identified, the bulk of which occur in the upstream promoter sequences of these genes, which in many cases results in differential in vitro expression of the respective pro- or anti-inflammatory gene product. Particular HLA polymorphisms result in well-defined associations with a large number of immunologically-mediated diseases, including some diseases with known dietary risk factors. For example, individuals of HLA-DQA1*0501, DQB1*0201 genotype have a greater than 200-fold increased risk of developing intolerance to dietary wheat gluten (coeliac disease), and additional HLA-related factors may influence the development of malignant lymphoma within pre-existing coeliac disease. Similarly, HLA-DRB1 alleles sharing a common sequence motif constitute the primary known genetic risk factor for rheumatoid arthritis. The influence of polymorphisms associated with differential cytokine expression on disease susceptibility is currently of much interest. Most attention has been focused on associations with susceptibility to benign immunologically-mediated diseases, including a number of gut diseases. However, recent work from our laboratory indicates that cytokine polymorphisms may influence susceptibility to and prognosis in a number of different cancers, including malignant melanoma skin cancer and solid tumours which may be influenced by diet, such as prostate cancer (collaboration with the CRC/BPG UK Familial Prostate Cancer study). In addition, preliminary work suggests that dietary modulation of expression levels of certain cytokines in healthy human subjects may be genotype dependent.

Arthritis, Rheumatoid↗
PubMed2002

A positive response to infliximab in Crohn disease: association with a higher systemic inflammation before treatment but not with -308 TNF gene polymorphism.

BACKGROUND: Two-thirds to three-fourths of patients with either refractory luminal or fistulizing Crohn disease respond to infliximab treatment. The ability or inability to respond seems to persist over time. Biological characteristics and/or genetic background can influence the response to treatment. The aim was to assess the value of C-reactive protein and TNF-alpha serum levels before treatment as well as the TNF -308 gene polymorphism in the prediction of response to infliximab treatment in Crohn disease. METHODS: Two-hundred-and-twenty-six Crohn disease patients treated in the setting of an expanded access programme to infliximab in Belgium were studied. There were 136 refractory luminal diseases and 90 refractory fistulizing diseases. Luminal diseases were treated with one single infusion; fistulizing diseases with three infusions at weeks 0, 2 and 6. A clinical response to treatment was defined as either a Crohn disease activity index <150 (complete) or a drop of 70 points (partial) at week 4, for luminal disease, and as either complete fistula healing (complete) or a decrease of at least 50% of the number of draining fistulas on two consecutive visits between weeks 0 and 18, for fistulizing disease. CRP and serum TNF-alpha levels were measured at week 0 before treatment and were compared between responders and non-responders. Patients were genotyped for the -308 TNF gene polymorphism, and allelic as well as genotype frequencies were compared between responders and non-responders. RESULTS: There were 73.2% responders (46.4% complete and 26.8% partial) and 26.8% non-responders. Response rates were similar in luminal and fistulizing diseases. CRP level before treatment was significantly higher in responders than in non-responders (16.8 mg/l (5-160) versus 9.6 mg/l (5-143); P = 0.02). Furthermore, response rate was significantly higher in patients with elevated CRP (>5 mg/l) than in patients with a normal CRP value (<5 mg/l) before treatment (76% versus 46%; P=0.004; OR: 0.26 (0.11-0.63)). Allelic and genotype frequencies for -308 TNF gene polymorphism were not significantly different between responders and non-responders--with the exception of a slightly higher TNF2 frequency in non-responders in luminal disease (22.1 % versus 11.6%; P = 0.04). However, this was not associated with a significant difference in genotype frequencies. CONCLUSION: A positive clinical response to infliximab was associated with a higher CRP level before treatment in our population of Crohn disease patients, but there was no relevant association with -308 TNF gene polymorphism. We therefore suggest that CRP level may help to identify better candidates for infliximab treatment.

Adolescent↗
PubMed1996

Vitamin D receptor gene polymorphisms are not related to bone turnover, rate of bone loss, and bone mass in postmenopausal women: the OFELY Study.

Vitamin D receptor (VDR) gene polymorphisms have been reported to account for most of the well established genetic influence on bone mineral density (BMD). However, discordant studies have been published and it is still not clear whether VDR genotypes influence bone mass accretion and/or postmenopausal bone loss. In this study, we analyzed VDR gene polymorphisms, i.e., that of BsmI, ApaI, and TaqI restriction enzymes in 268 untreated postmenopausal women 1-26 years postmenopausal. There were 37 BBAA homozygote (absence of BsmI and ApaI restriction sites on both alleles), 55 bbaa homozygote (presence of restriction sites on both alleles), and 176 heterozygotes. At baseline, women between the three genotypes did not differ significantly in age, years since menopause, body mass index (BMI), nor dietary calcium intake. We found no relationship between VDR genotypes and bone turnover assessed by three serum markers of bone formation and three urinary bone resorption markers, nor with BMD measured at the spine, hip, forearm, and whole body by dual-energy X-ray absorptiometry (DXA). Rates of bone loss assessed by repeated DXA measurements over 2 years were highly significant (p = 0.02-0.0001) at all skeletal sites except for the lumbar spine but did not differ between genotypes at any sites either before or after adjustment for potential confounding factors such as years since menopause, BMI, calcium intake, serum 25 hydroxyvitamin D levels, and baseline BMD. When we restricted the analysis to early postmenopausal women, within 10 years of menopause (n = 128), lumbar spine bone loss became significant, but no significant difference between VDR genotypes in the rate of bone loss measured at any site was found. We conclude that VDR genotypes are not predictive of bone turnover, rate of postmenopausal bone loss, and bone mass in either early or late postmenopausal women. In a subgroup of women with a low calcium intake (below 600 mg/day), we also found no significant differences between genotypes in BMD and the rate of bone loss measured at any site, although the sample size (n = 64) may be too small to detect small differences. In conclusion, these data, along with the absence of relationships between VDR gene polymorphisms and peak bone mass that we recently reported, suggest that the determination of VDR genotypes is probably not a useful clinical test for the risk assessment of osteoporosis.

Absorptiometry, Photon↗
PubMed2001

Vitamin D receptor gene polymorphism and bone mineral density in patients with type 2 diabetes mellitus.

OBJECTIVE: To explore the relationship between vitamin D receptor (VDR) gene polymorphisms and bone mineral density (BMD) in patients with type 2 diabetes mellitus (DM) and to better understand the pathogenesis of osteoporosis. METHODS: Ninety seven patients with type 2 DM were recruited for this study. BMD was measured by single photon absorptiometry at the lower one third of the nondominant radius and ulna. Polymorphisms of the VDR gene were analyzed by DNA amplification with polymerase chain reaction (PCR) and endonuclease digestion with Bsm I. RESULTS: The respective frequencies of VDR genotypes were BB 18.6%, Bb 27.8% and bb 53.6%. The Z scores of the three groups were -1.57 +/- -0.60, -1.45 +/- -0.67 and -1.41 +/- -0.81, respectively. Although the BMD of the Bb genotype DM patients was higher than that of BB genotype DM patients and lower than that of bb genotype DM patients, there were no significant differences. CONCLUSION: These findings suggest a small influence of VDR gene polymorphism on the BMD of patients with type 2 DM. Further study on the value of VDR genotypes in the pathogenesis of osteoporosis in diabetes mellitus is still needed.

Adult↗
PubMed2004

Alzheimer disease risk associated with APOE4 is modified by STH gene polymorphism.

The association of the STH gene polymorphism with Alzheimer disease (AD) is debated. In the analysis of two genetically and diagnostically distinct groups of Alzheimer patients from the USA and Italy, the authors did not find an association with the STH polymorphism. However, the APOE-4-associated risk of AD greatly increased if the STH-G allele was also present. The STH-G allele appears to be a risk modifier for AD.

Aged↗
PubMed2003

Cytochrome P450 1A1 and manganese superoxide dismutase genes polymorphisms in ankylosing spondylitis.

OBJECTIVES: To investigate the associations of cytochrome p450 1A1 (CYP1A1) and manganese superoxide dismutase (MnSOD) genes polymorphisms with the susceptibility to AS in Taiwan. METHODS: The polymorphisms of CYP1A1 and MnSOD genes were determined in 70 patients with ankylosing spondylitis (AS) and 93 healthy controls by polymerase chain reaction (PCR)/restriction fragment length polymorphisms (RFLP) methods. RESULTS: The genotype frequency of CYP1A1 4887C/A was significantly lower in patients with AS than in controls. The phenotype frequency of CYP1A1 4887A also tended to be decreased in patients with AS. There were no significant differences in the genotype, allele, and phenotype frequencies of MnSOD gene polymorphisms between patients with AS and controls. CONCLUSION: CYP1A1 4887A may be a protective factor for the development of AS in Taiwan. However, MnSOD gene polymorphisms are not associated with the susceptibility to AS.

Cytochrome P-450 CYP1A1↗