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PubMed2002

Relationship between TaqIB cholesteryl ester transfer protein gene polymorphism and macrovascular complications in Japanese patients with type 2 diabetes.

Cholesteryl ester transfer protein (CETP) is a key regulating factor of lipid metabolism, and the polymorphism of its gene may therefore be a candidate for modulating the lipid parameters, altering the susceptibility to atherosclerosis in type 2 diabetic subjects. In a group of 443 unrelated Japanese patients with type 2 diabetes, we studied the B1B2 polymorphism at the CETP locus, which is detectable with the restriction enzyme TaqI. Patients were separated into three groups according to genotype and compared based on their clinical characteristics, lipid parameters, and macrovascular complications. The B2 allele was associated in a dose-dependent fashion with higher HDL cholesterol and apolipoprotein AI levels, together with lower CETP concentrations. Furthermore, the prevalence of macrovascular complications, such as coronary heart disease, arteriosclerosis obliterans, and cerebral vascular disease, was significantly higher in subjects with the B1B1 genotype. Multiple logistic regression analysis also showed that the B1 allele of CETP genotype was associated with the incidence of these three complications independently of other risk factors. Thus, in type 2 diabetic patients, the B1B2 polymorphism of CETP gene is likely to be a strong genetic predictor of macrovascular complications.

Alleles↗
PubMed2006

Association between androgen receptor gene polymorphism and bone density in older women using hormone replacement therapy.

OBJECTIVE: The objective of this study was to investigate the relationship between bone mineral density (BMD) and both CAG repeat polymorphism of the androgen receptor (AR) gene and skewed X chromosome inactivation (SI) in postmenopausal women. METHODS: BMD was measured by DEXA. Both the number and the X-weighted biallelic mean of the CAG repeats of AR were analysed by PCR, before and after DNA digestion with methylation-sensitive HpaII in 192 healthy Caucasian postmenopausal women. RESULTS: The number of CAG repeats ranged from 10 to 34, with a median value of 22. CAG)(n< or =22) and CAG)(n> or =23) alleles were designated as short and long alleles, respectively. In women using hormone replacement therapy (HRT) (n=81), lumbar spine BMD was significantly lower, and femoral neck and total body BMD marginally lower in those with long-long alleles when compared with those with other genotypes. SI (> or =80%) was observed in 24% of the women and was not associated with BMD. In women using HRT, femoral neck BMD was significantly lower, and lumbar spine and total body BMD marginally lower in those whose X-weighted CAG repeat biallelic was greater than 22.59 (median value) when compared to other genotypes. These results were not found in women not using HRT. CONCLUSION: In conclusion, our results suggest that BMD may be associated with AR gene polymorphism in postmenopausal women using HRT but not with SI. Further studies are needed to investigate the mechanisms of the interaction between HRT, BMD and AR found in the present study.

Absorptiometry, Photon↗
PubMed2003

Plasminogen activator inhibitor-1 4G/5G gene polymorphism in patients with myocardial or cerebrovascular infarction in Tianjin, China.

OBJECTIVE: To investigate the association between the plasminogen activator inhibitor-1 (PAI-1) 4G/5G gene polymorphism and the occurrence of myocardial and cerebrovascular infarctions in individuals from Tianjin, China. METHODS: The PAI-1 genotype was determined using allele-specific polymerase chain reaction (AS-PCR) in 56 myocardial infarction (MI) patients, 54 cerebrovascular infarction (CI) patients and 83 unrelated healthy controls. All subjects' clinical features and plasma PAI-1 activity levels were determined. RESULTS: The PAI-1 genotype distribution frequency of the single guanine deletion/insertion 4G/5G polymorphism (located -675 bp upstream from the start of transcription) significantly differed between the patients and healthy controls. In the MI group, the 4G/4G-genotype frequency was increased, but the 4G/5G-genotype is decreased when compared to the control group. In the CI group, both the 4G/4G- and 4G/5G -genotypes occurred at a lower frequency than those in the control group (P < 0.001). The plasma PAI-1 activity level in the MI group was lowered as the presence of the 4G allele decreases. In the CI group, the frequency of 5G/5G was much higher than that of the control group (P < 0.001). The plasma PAI-1 activity level in the CI group was elevated as the presence of the 5G allele increased. Furthermore, positive correlation between triglyceride, glucose levels and PAI-1 activity were found in all three groups (P < 0.001). CONCLUSIONS: The PAI-1 4G/5G gene polymorphism is associated with a higher risk of MI and CI in individuals in Tianjin, China. The deletion/insertion polymorphism is probably an important hereditary risk factor for heart diseases. Moreover, triglyceride and glucose levels of plasma have functional importance in regulating PAI-1 activity.

Aged↗
PubMed2003

Possible association between -G308A tumour necrosis factor-alpha gene polymorphism and major depressive disorder in the Korean population.

OBJECTIVE: The present study was aimed at examining the association between the -G308A tumour necrosis factor-alpha gene polymorphism and major depressive disorder (MDD) in the Korean population. METHODS: One hundred and eight in-patients with MDD and 125 healthy controls participated in this study. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: Genotype and allele distributions in patients with MDD (P=0.024 and P=0.0125, respectively), were significantly different from those of the controls. In particular, subjects with MDD had an increased frequency of the TNF2 (A) allele. CONCLUSION: The present study suggests that the -G308A tumour necrosis factor-alpha gene polymorphism may have a potential role for susceptibility to MDD in the Korean population.

Asian People↗
PubMed2003

Association of two angiotensinogen gene polymorphisms, M235T and G(-6)A, with chronic heart failure.

The aim of the study was to focus on the relationship between the angiotensinogen (AGT) gene polymorphisms, M235T and promoter G(-6)A, and chronic heart failure in the Czech population. A total of 158 patients with chronic heart failure (functional class NYHA II-IV, ejection fraction <40%, cardiothoracic index >50%) were compared with a control group of 200 subjects of similar age and sex distribution, without any personal history of cardiovascular diseases. The AGT gene polymorphisms were detected by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) methods. No significant differences in distributions of AGT genotypes between patients with chronic heart failure (CHF) and controls were found. The differences in distributions of alleles in AGT M235T (P(a)=0.02) and genotypes in AGT G(-6)A (P(g)=0.017) were found within women groups. Within CHF patients the distribution of AGT G(-6)A genotypes was not consistent with Hardy-Weinberg equilibrium (P=0.0001). We found significant relative risk of CHF in the GGMT genotype, OR=2.63 with 95% CI 1.39-4.95, P(corr)=0.01 (in the male group OR=1.83, 95% CI 0.92-3.66, P(corr)=0.3; in the female group OR=15.5, 95% CI 1.86-129.42, P(corr)=0.008). We provide evidence of increased risk in subjects with the GGMT variant of associated genotype of AGT gene for CHF, especially of fifteen-fold risk of this variant in women.

Adult↗
PubMed1999

[The relationship between apolipoprotein E gene polymorphism and coronary heart disease and arteriosclerotic cerebral infarction].

OBJECTIVE: To detect the relationship between ApoE gene polymorphism and coronary heart disease(CHD), arteriosclerotic cerebral infarction(ACI). METHODS: Exon 4 of ApoE gene was analyzed in normal group(87 cases), CHD group(78 cases) and ACI group(55 cases) by a combination of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct AgNO(3) staining technique. RESULTS: Between the control group and CHD group, ACI group, chi(2) test showed no significant difference in genotype of E3/E3 (P>0.5, P>0.1, respectively); while mu test showed no significant difference in allele epsilon(2)(P>0.25, P>0.1, respectively), epsilon(4)(P>0.1, P>0.25, respectively) of ApoE. CONCLUSION: No relationship between ApoE gene polymorphism and CHD and ACI was noted in this study.

Apolipoproteins E↗
PubMed2004

Contribution of MHC class I chain-related A (MICA) gene polymorphism to genetic susceptibility for systemic lupus erythematosus.

OBJECTIVE: To evaluate the contribution of the MHC class I chain-related A (MICA) gene polymorphism to the genetic risk of systemic lupus erythematosus (SLE). METHODS: HLA-DRB1-DQA1-DQB1 genotyping, MICA exon 5 microsatellite genotyping and HLA-B8 genotyping were performed in 48 Italian SLE patients and in 158 healthy control subjects. RESULTS: Of HLA class II haplotypes, only DRB1*03-DQA1*0501-DQB1*0201 (DR3-DQ2) was significantly more frequent among SLE patients than among healthy control subjects [odds ratio (OR) = 6.5, corrected P < 0.0026]. HLA-B8 was detected in 31% SLE patients and 13% healthy control subjects (OR = 3.0, P = 0.005). The allele-wise comparison between patients and controls showed that both MICA5 (OR = 2.5, corrected P < 0.0005) and MICA5.1 (OR = 2.4, corrected P < 0.0005) were positively and MICA9 (OR = 0.2, corrected P < 0.0005) was negatively associated with the disease. The MICA5/5.1 genotype was positively associated with SLE (OR = 28.9, corrected P < 0.0015) also in subjects negative for DR3-DQ2 (OR > 22.6, corrected P < 0.011). The simultaneous presence of DR3-DQ2 and MICA5.1 was detected in 15/48 (31%) SLE and in 10/158 (6%) healthy control subjects (OR = 6.7, corrected P < 0.011). The simultaneous combination of DR3-DQ2 and MICA5 was found in 10/48 (21%) SLE patients and in only 1/158 healthy control subjects (OR = 41.3, corrected P < 0.011). Logistic regression analysis showed the independent positive associations of MICA5 and MICA5.1 and negative association of MICA9 with the disease, and revealed that the interaction of the three major markers (DR3-DQ2, MICA5 and MICA5.1) was associated with increasing genetic risk, which was highest (OR > 30.3) in DR3-DQ2-positive subjects carrying the MICA5-5.1 genotype. CONCLUSIONS: Our study provides the first demonstration of the independent association of the MICA gene polymorphism with genetic risk of SLE.

Adult↗
PubMed2006

Genetic alterations in chromosome 10q24.3 and glutathione S-transferase omega 2 gene polymorphism in ovarian cancer.

The molecular basis of ovarian cancer development has not been fully elucidated. In this study, genetic alterations in ovarian cancer were identified by arbitrarily primed polymerase chain reaction (AP-PCR). A gene in DNA fingerprinting, amplified from primer AE11, was cloned, sequenced, and identified by comparison with known genes in the genome database. Gene amplification in chromosome 10q24.3 was identified and measured by real-time PCR. Three out of 20 cases harbored this gene amplification. This amplified region was identified as IVS-4 of the glutathione-S-transferase Omega 2 (GSTO2) gene. Therefore, the mutations in all 6 exons of the GSTO2 gene were determined. The A to G transition at codon 142 in exon 4 (AAT to GAT, N142D) was observed. The frequency of GSTO2 gene polymorphism was analyzed in 20 ovarian cancers, compared with 41 normal individuals. The gene frequencies of D142 and N142 allele in ovarian cancer cases were 0.3 and 0.7, whereas in normal females, they were 0.2 and 0.8, respectively. The odds ratio of D142 allele in ovarian cancer was 1.73 (95% CI = 0.51-5.89), indicating that this GSTO2 gene polymorphism may be associated with the risk of ovarian cancer.

Chromosomes, Human, Pair 10↗
PubMed2005

Tumor necrosis factor gene polymorphisms and clearance or progression of hepatitis B virus infection.

OBJECTIVES: We evaluated the influence of tumor necrosis factor-alpha (TNF-alpha) promoter gene polymorphisms on clearance of hepatitis B virus (HBV) and outcome of HBV chronic hepatitis. METHODS: Four TNF-alpha promoter polymorphisms (T-1031C, C-863A, G-308A, and G-238A) were evaluated by direct sequencing in 184 chronic HBV carriers hepatitis B surface antigen (HBsAg) positive and 96 controls with documented sero-clearance (HBsAg negativity, positivity for anti-HBs and anti-HBc IgG). Frequencies of single-nucleotide polymorphisms (SNPs) and haplotypes in the control group were compared with those of the chronic carrier group and with clinically defined subgroups of the latter: asymptomatic carriers, patients with compensated hepatitis, decompensated cirrhotics, and patients with hepatocellular carcinoma. Furthermore, subgroups of chronic carriers were compared among them. RESULTS: In the chronic carrier group, the -308 G allele was more frequent in those with a family history of HBV infection (96% vs 88% of those with non-familial transmission). The G/G genotype at position -308 was found in all chronic carriers with decompensated cirrhosis but in only 78% of controls (P=0.01) and was more frequent in decompensated cirrhotics than in the other subgroups. The distribution of TNF-alpha gene polymorphisms in the carrier group was not significantly different from that in the sero-clearance control group. TNF-alpha SNPs at positions -1031/-863 and -863/-238 were in linkage disequilibrium. The TCGG haplotype (-T1031, -C863, -G308, -G238) was significantly associated with end-stage liver disease. CONCLUSION: The TNF-alpha promoter polymorphisms do not appear to be determinant of HBV sero-clearance in southern Italians. The genotype -308G/G and haplotype TCGG are associated with an unfavorable prognosis in patients with chronic HBV infection.

Carrier State↗
PubMed2006

Gene-environment interaction involved in oral carcinogenesis: molecular epidemiological study for metabolic and DNA repair gene polymorphisms.

BACKGROUND: Exposure to environmental carcinogens leads to oral squamous cell carcinoma (OSCC); however, the impact of genetic variations in carcinogen metabolisms and DNA repair on OSCC risk considering environmental exposures has not been clearly elucidated. METHODS: We conducted a case-control study with 122 cases and 241 controls. The risk of OSCC was evaluated in 10 genetic polymorphisms of nine genes, such as CYP1A1, CYP2E1, GSTM1, GSTT1, XPA, XPC, XPC, XPF and ERCC1. Gene-environment interaction was also evaluated. RESULTS: We found that CYP2E1 and XPA polymorphisms significantly affected the OSCC risk. Gene-environment interactions with smoking were significant for CYP2E1 and ERCC1 polymorphisms. Odds ratios for gene-environment interaction were 7.98 (P = 0.036), 9.67 (P = 0.017) and 8.49 (P = 0.031) for CYP2E1RsaI, DraI and ERCC1 polymorphisms, respectively. No interaction was observed with heavy drinking and any polymorphisms. CONCLUSION: CYP2E1, XPA and ERCC1 polymorphisms may affect the risk of OSCC.

Alcohol Drinking↗
PubMed2004

Tacrolimus dosing in adult lung transplant patients is related to cytochrome P4503A5 gene polymorphism.

Tacrolimus is a potent immunosuppressive agent used in lung transplantation and is a substrate for both P-glycoprotein (P-gp, encoded by the gene MDR1) and cytochrome (CYP) P4503A. A previous study by the authors identified a correlation between the tacrolimus blood level per dose with CYP3A5 and MDR1 gene polymorphisms in pediatric heart transplant patients. The objective of this study was to confirm the influence of these polymorphisms on tacrolimus dosing in adult lung transplant patients. Adult lung transplant patients who had been followed for at least 1 year after lung transplantation were studied. Tacrolimus blood level (ng/mL) per dose (mg/day) at 1, 3, 6, 9, and 12 months after transplantation was calculated as [L/D]. DNA was extracted from blood. MDR1 3435 CC, CT, and TT; MDR1 2677 GG, GT, and TT; and CYP3A5*1 (expressor) and *3 (nonexpressor) genotypes were determined by PCR amplification, direct sequencing, and sequence evaluation. Eighty-three patients were studied. At 1, 3, 6, 9, and 12 months after the transplant, a significant difference in [L/D] was found between the CYP3A5 expressor versus nonexpressor genotypes (mean +/- SD of 1.49 +/- 0.88 vs. 3.11 +/- 4.27, p = 0.01; 1.23 +/- 0.82 vs. 3.44 +/- 8.97, p = 0.05; 1.32 +/- 0.96 vs. 3.81 +/- 6.66, p = 0.005; 0.95 +/- 1.19 vs. 3.74 +/- 5.98, p = 0.0015; and 0.45 +/- 0.2 vs. 3.76 +/- 6.75, p = 0.0001, respectively). MDR1 G2677T and C3435T genotypes had only minimal effects on [L/D] at 1 and 3 months after transplantation. This study confirms the relationship of CYP3A5 polymorphisms to tacrolimus dosing in organ transplant patients. CYP3A5 expressor genotypes required a larger tacrolimus dose to achieve the same blood levels than the CYP3A5 nonexpressors at all time points during the first posttransplant year. This was not uniformly true for MDR1. The authors therefore conclude that tacrolimus dosing in adult lung transplant patients is associated with CYP3A5 gene polymorphisms.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

Aldose reductase (AC)n gene polymorphism and susceptibility to diabetic retinopathy in Type 2 diabetes in Caucasians.

Genetic factors are implicated in the development of diabetic retinopathy, and the aldose reductase (AC)n gene is a candidate gene for the development of diabetic retinopathy in patients with Type 2 diabetes. In the association study, a relationship between the aldose reductase (AC)n gene polymorphism and the development of diabetic retinopathy in patients with Type 2 diabetes were studied. We tested the hypothesis whether the Z-2 allele of the aldose reductase gene is a risk factor for the development of diabetic retinopathy in a group of Caucasian participants with Type 2 diabetes. Two hundred and five participants with Type 2 diabetes were enrolled in the study: 124 participants with Type 2 diabetes with diabetic retinopathy were compared with 81 diabetic participants without retinopathy with diabetes duration of more than 10 years. Eight alleles of the aldose reductase (AC)n gene polymorphism were detected: Z+6, Z+4, Z+2, Z, Z-2, Z-4, Z-6, and Z-8. An increased frequency of the Z-2 allele was found in the patients with diabetic retinopathy compared with the patients without diabetic retinopathy (39.1% vs. 26.5%; P value=.009, chi2=6.9). Our results suggest that the Z-2 allele of the aldose reductase gene is a risk factor for the development of diabetic retinopathy in a group of Caucasian participants with Type 2 diabetes.

Aged↗
PubMed1999

Possible genetic association between interleukin-1alpha gene polymorphism and the severity of chronic polyarthritis.

Interleukin-1 (IL-1) has been implicated in the pathogenesis of rheumatoid arthritis (RA). IL-1alpha gene polymorphism was analysed for the exon V and promoter region in 51 patients with destructive and 47 with non-destructive RA, as well as in 94 controls. The two biallelic polymorphisms in the promoter region and the exon V were 100% linked. The rare IL-1A2 allele carriage rate was 45% in the control population. It was increased in destructive (54.4%) and decreased in non-destructive RA (26.8%, destructive versus non-destructive, p < 0.007). All indices of disease activity and joint destruction were significantly lower in the patients positive for IL-1A1, and higher in those positive for IL-1A2. The present findings suggest that this IL-1alpha gene polymorphism may contribute to the pathogenesis of chronic polyarthritis. The presence of the IL-1A2 allele could constitute a risk factor for the development of destructive arthritis and could be used early in the course of the disease as a prognostic marker.

Alleles↗
PubMed2003

Glanzmann's thrombasthenia: modulation of clinical phenotype by alpha2C807T gene polymorphism.

BACKGROUND AND OBJECTIVES: The expression of Glanzmann's thromboasthenia (GT) varies, even among patients carrying the same mutation. It is conceivable that other gene loci may influence the clinical expression of GT and lead to specific phenotypes. DESIGN AND METHODS: To investigate GT clinical heterogeneity we screened 25 GT patients with a known alpha(IIb)beta3 molecular defect for thrombophilic mutations (FV Leiden, FII A20210) and the platelet glycoprotein (GP) alpha2 C807T gene polymorphism. RESULTS: The FV Leiden mutation was found in 1 patient, the FII A20210 mutation in none. Three GT patients were homozygous for the T807 allele and showed a mild clinical expression of GT whereas none of the patients presenting with a moderate or severe GT phenotype carried the alpha2 TT genotype (p=0.037, two-sided exact test). In patients carrying the same mutation, the clinical GT phenotype was milder in those with the TT807 genotype. INTERPRETATION AND CONCLUSIONS: Since the platelet alpha2 C807T gene polymorphism is associated with alpha2beta1 receptor density on the platelet surface, our findings suggest that the level of alpha2beta1 on platelets may be an additional factor affecting GT clinical expression.

3' Untranslated Regions↗
PubMed2000

Positive association of endothelial nitric oxide synthase gene polymorphism with hypertension in northern Japan.

Vascular endothelial cells produce nitric oxide (NO), which contributes to the regulation of blood pressure and regional blood flow. Although Endothelial NO synthase (eNOS) gene polymorphisms have been shown to have a positive association with coronary artery disease, the linkage between eNOS gene polymorphisms and hypertension has been controversial. In the present study, therefore, we identified genotypes for Glu298Asp and variable number tandem repeats in intron 4 (4b/a) in 183 hypertensive and 193 normotensive populations. The Glu298Asp variant had a significant association with hypertension (odds ratio, 1.8; 95% confidence interval, 1.1-3.0). The allele frequencies of 298Asp for Glu298 in hypertensive patients were significantly higher than those in normotensive subjects (0.128 vs 0.080, p<0.05). Diastolic and mean arterial blood pressures were significantly higher in hypertensive subjects with the 298Asp allele than those without the variant allele (p<0.05). However, disequilibrium of 4b/a polymorphism was absent between these two groups. These results suggest that the Glu298Asp variant may be a genetic susceptibility factor for hypertension.

Aged↗
PubMed2006

Increased prevalence of interleukin-1 receptor antagonist gene polymorphism in patients with chronic rhinosinusitis.

OBJECTIVE: To assess the association of the interleukin (IL)-1beta and the IL-1 receptor antagonist (IL-1Ra) gene polymorphisms with chronic rhinosinusitis (CRS). DESIGN: Genotyping of the 2 IL-1beta gene (IL1B) polymorphisms (promoter and exon) and the IL-1Ra gene (IL1RN) polymorphism (intron 2) was performed using polymerase chain reaction and restriction length fragment polymorphism analyses. SETTING: Prospective study, tertiary medical center. PATIENTS: The study population comprised 88 consecutive adult Taiwan-Chinese patients who met stringent criteria for CRS and received endoscopic sinus surgery and 103 healthy volunteers of the same ethnicity and similar age range. Of the 88 patients, 61 had CRS with nasal polyps, while the other 27 had CRS without nasal polyps. RESULTS: There were significant differences in the distribution of the IL1RN polymorphism between the control subjects and patients with CRS (P<.05). The II allele of IL1RN occurred more frequently in the CRS patient group, and the odds ratio for subjects with I/II genotype was 3.39 (95% confidence interval, 1.25-9.18). In the case of CRS without nasal polyps, the odds ratio for subjects with I/II genotype was further increased to 4.75 (1.39-16.25). There was no association between the other 2 polymorphisms of IL1B and CRS. CONCLUSION: Increased prevalence of IL1RN polymorphism in patients with CRS suggests that this polymorphism, or a polymorphism in linkage disequilibrium with it, may be involved in the development of CRS.

Adult↗
PubMed2006

TGF-beta1 gene polymorphism in liver graft recipients.

Cytokines are known to be important mediators during liver graft outcome and their gene polymorphism could affect the overall expression and secretion of cytokines. In this retrospective study, we analyzed the effect of TGF-beta1 polymorphism in 150 liver allograft recipients. Genotyping PCR-SSP were performed for TGF-beta1 gene (codon 10T/C and 25C/G). TGF-beta1 polymorphism at codon 10 and 25 correlate borderline with liver graft acceptance and when the combination between codon 10 and 25 was analyzed, it revealed that T/T G/C genotype and the TC haplotype were significantly associated with graft acceptance (p<0.05). TGF-beta1 high secretor phenotype was also increased in the acute rejection group close to significance (p=0.06). In conclusion, these findings show a correlation between TGF-beta1 gene polymorphism and liver graft acceptance.

Codon↗
PubMed1998

Vitamin D receptor gene polymorphism is associated with metastatic breast cancer.

The vitamin D receptor (VDR) has been detected in breast tumor cells. We tested the hypothesis that VDR gene polymorphism might influence the outcome of women affected by breast cancer. A total of 88 breast cancer patients were recruited: 50 women were affected by newly diagnosed breast cancer whereas 38 women suffered from relapsing disease. The individual genetic pattern for VDR was evaluated by DNA extraction followed by PCR amplification of the VDR gene, and digestion with the restriction enzyme BsmI. In 167 healthy women, participating in the osteoporosis prevention trial and being used as a control, we detected 121 Bb heterozygotes (72%), 26 homozygotes for the bb alleles (16%), and 20 homozygotes for the BB alleles (12%). In the newly diagnosed breast cancer group the occurrence of Bb patients was 58% (29/50); bb patients represented 22% (11/50), and BB cases were 20% (10/50). The VDR frequency distribution in the control and primary disease patient groups was not statistically different. In the metastatic cancer group, the prevalence of the bb genotype (14/38; 37%) was double the percentage of control subjects, whereas the percentage of BB women with metastases was half the control group (2/38; 5%). Women who were homozygous bb appeared to have almost a four times higher risk of developing metastases than BB women. Whatever the molecular mechanisms underlying the VDR effects in cancer cells, we believe that the VDR gene polymorphism may represent an important determinant in the evaluation of women affected by breast cancer and might help design targeted therapy.

Alleles↗