Cytochrome P450 (CYP) 7B1 is involved in many metabolic processes including androgen metabolism. Genetic variation in the CYP7B1 gene may play a role in predisposition to prostate cancer. Here, we screened the human CYP7B1 gene for possible polymorphisms. Only one single polymorphism was detected, a C-G change in the promoter -104 base pair from the transcription start site. The allele frequency was investigated in Swedish men and compared to a Korean population, as it is known that the frequency of prostate cancer is low among Orientals. We found that the frequency of the G-allele was 4.04% in Swedes (n ¼ 150) but only 0.33% among Koreans (n ¼ 153). Computer analysis indicated that the two variants bind with different affinities to a CCAAT-box binding protein. Expression studies with reporter constructs showed significantly higher transcriptional activity of the G variant in Hek293 cells (2.7-fold, Po0.05). In conclusion, we report here for the first time the detection of a single polymorphism in the CYP7B1 gene. This polymorphism is associated with phenotypic differences in an expression system and a widely different allele frequency in two ethnic populations, with great differences in the incidence of prostate cancer.

Association between the histidine-rich glycoprotein (HRG) C633T single nucleotide polymorphism (SNP) and recurrent miscarriage was investigated in a case-control study. The cases constituted 187 women with recurrent miscarriage that were compared with 395 controls who had delivered a child and had no history of miscarriage. Blood samples were collected from each woman, genomic DNA was extracted and genotyped for the HRG C633T SNP. In the whole study population, the percentage of miscarriage was the same, regardless of genotype (C/C 31.2%, C/T 32.9% and T/T 32.5%). However, an association between homozygous T/T carriers and recurrent miscarriage was detected in a subgroup of women with primary recurrent miscarriage (odds ratio 2.44, 95% CI 1.01-5.92). Our results indicate an important role for the HRG C633T SNP in the occurrence of recurrent miscarriage.

BackgroundHistidine-rich Glycoprotein (HRG) has previously been shown to have an impact on implantation and fertility. The aim of this study was to investigate if there is an association between the HRG A1042G single nucleotide polymorphism (SNP) and recurrent miscarriage.MethodsThe study was designed as a case-control study and the women were included at University Hospitals in Sweden. 186 cases with recurrent miscarriage were compared with 380 pregnant controls with no history of miscarriage. Each woman was genotyped for the HRG A1042G SNP.ResultsThe results indicated that the frequency of heterozygous HRG A1042G carriers was higher among controls compared to cases (34.7% vs 26.3%; p < 0.05). In a bivariate regression analysis, a negative association was found between recurrent miscarriage and heterozygous A/G carriers both in the entire study population (OR 0.67, 95% CI 0.45 - 0.99; p < 0.05) as well as in a subgroup of women with primary recurrent miscarriage (OR 0.37, 95% CI 0.16 - 0.84; p < 0.05). These results remained even after adjustment for known confounders such as age, BMI and thyroid disease (OR 0.36, 95% CI 0.15 - 0.84; p < 0.05).ConclusionsWomen who are heterozygous carriers of the HRG A1042G SNP suffer from recurrent miscarriage more seldom than homozygous carriers. Thus, analysis of the HRG A1042G SNP might be of importance for individual counseling regarding miscarriage.

Background: Human 17β-hydroxysteroid dehydrogenase type 5 (17β-HSD5) formally known as aldo-keto reductase 1C3 (AKR1C3) play a major role in the formation and metabolism of androgens. The enzyme is highly expressed in the prostate gland and previous studies indicate that genetic variation in the AKR1C3 gene may influence the prostate volume and risk of prostate cancer. Aim: Here we aimed to further study the genetic regulation of AKR1C3 and its putative role in prostate cancer. Experiments: A previously identified promoter polymorphism (A>G, rs3763676) localized at −138 from the translational start site were studied in relation to prostate cancer in a Swedish population based case–control study including 176 patients diagnosed with prostate cancer and 161 controls. Moreover, we have studied the basal and androgen induced promoter activity of the AKR1C3 gene. Expression studies with AKR1C3 promoter reporter constructs were performed in HepG2 and DSL2 cells. Results: We found that carriers of the promoter A-allele had a borderline significant decreased risk of prostate cancer (OR = 0.59; 95% CI = 0.32–1.08). We also show that dihydrotestosterone (DHT) induced the promoter activity of the A-allele 2.2-fold (p = 0.048). Sp3 seem to play an important role in regulating the transcription activity of AKR1C3 and site-directed mutagenesis of a GC-box 78 base-pair upstream the ATG-site significantly inhibited the basal AKR1C3 promoter activity by 70%. Conclusion: These results further supports previous findings that the A>G promoter polymorphism may be functional and that AKR1C3 plays a critical role in prostate carcinogenesis. Our findings also show that the members of Sp family of transcription factors are important for the constitutive expression of AKR1C3 gene.