This study aimed to investigate the correlations among androgen receptor (AR) CAG repeat polymorphism, sex hormones and penile length in healthy Chinese young adult men. Two hundred and fifty-three healthy men (age...This study aimed to investigate the correlations among androgen receptor (AR) CAG repeat polymorphism, sex hormones and penile length in healthy Chinese young adult men. Two hundred and fifty-three healthy men (aged 22.8 ± 3.1years) were enrolled. The individuals were grouped as CAG short (CAGs) if they harbored repeat length of 〈20 or as CAG long (CAGL) if their CAG repeat length was 〉20. Body height/weight, penile length and other parameters were examined and recorded by the specified physicians; CAG repeat polymorphism was determined by the polymerase chain reaction (PCR) method; and the serum levels of the sex hormones were detected by radioimmunoassay. Student's t-test or linear regression analysis was used to assess the associations among AR CAG repeat polymorphism, sex hormones and penile length. This investigation showed that the serum total testosterone (T) level was positively associated with the AR CAG repeat length (P = 0.01); whereas, no significant correlation of T or AR CAG repeat polymorphism with the penile length was found (P = 0.593). Interestingly, an inverse association was observed between serum prolactin (PRL) levels and penile length by linear regression analyses (β = -0.024, P = 0.039, 95% confidence interval (CI): -0.047, 0). Collectively, this study provides the first evidence that serum PRL, but not T or AR CAG repeat polymorphism, is correlated with penile length in the Han adult population from northwestern China.展开更多
Objective:To explore the relation between the polymorphism of repetitive sequence in gene CAG of androgen receptor(AR)and the susceptibility and clinical stages as well as pathological grading of prostate cancer among...Objective:To explore the relation between the polymorphism of repetitive sequence in gene CAG of androgen receptor(AR)and the susceptibility and clinical stages as well as pathological grading of prostate cancer among Han population.Method:Sixty-eight cases with prostate cancer hospitalized in Urinary Surgery Department from Feb.2010 to Feb.2012 and 60 healthy cases were chosen as research subjects.Methods of PCR and direct sequencing were adopted to detect DNA sequence of AR gene and the length of repetitive sequence in CAG.Results:The lengths of repetitive sequence in CAG of patients with prostate cancer and healthy people were(22.3±4.6)and(23.0±4.9),respectively showing no statistical significance.Comparing length(repetitive sequence of CAG)>22,those with that<22 suffer a remarkably higher risk of prostate cancer(P<0.05).The number of repetitive sequence in CAG of patients at clinical stage C-D was less than that of patients at stage B,and the number of repetitive sequence in CAG of patients with poorly differentiated prostate cancer was also less than that of patients with moderately and highly differentiated prostate cancer.But there was no statistical significance int the difference(P>0.05);the proportion of patients with length<22 at clinical stage C-D was much larger than that of patients at clinical stage B(P<0.05),and as the aggravation of pathological grading,the proportion of patients with the length<22 was also remarkably increased and there was significant difference between patients with highly differentiated prostate cancer and those with poorly differentiated prostate cancer(P<0.05).Conclusions:There is correlation between the occurrence and development of prostate cancer in Han population and the polymorphism of repetitive sequence in gene CAG of androgen receptor.The less the number of repetitive sequence in CAG is,the higher the risk of prostate cancer will be and the more severe the clinical stage and pathological grading will be.展开更多
Aim: The Androgen Receptor (AR) is a ligand-dependent transcriptional activator and the AR gene contains a highly polymorphic trinucleotide repeat CAG and GGN in the first exon. Given the lack of information AR-CAG an...Aim: The Androgen Receptor (AR) is a ligand-dependent transcriptional activator and the AR gene contains a highly polymorphic trinucleotide repeat CAG and GGN in the first exon. Given the lack of information AR-CAG and GGN repeat polymorphism and its potential correlation with breast cancer in South Indian women, we conducted a case-control study to observe the effects of CAG & GGN repeat length polymorphism and risk of breast cancer. Methods: Polymorphisms for AR-CAG and GGN repeat length was detected by Gene Scan analysis in the genomic DNA from cases with breast cancer and controls. Results: Association between AR genotype was calculated by categorising alleles as short (S) and long (L) and taking median value as the cut-off. LL genotype of CAG repeat was found to be associated with breast cancer (OR, 4.58;95% CI, 10.61-1.98;p—0.0004). GGN repeat having ≥21 was found in most of the cases and none of the cases showed 20 repeats thus indicate that alleles having homozygous repeat 20 may be protective towards breast cancer. Also, SS genotype was observed in 56.84% of cases and in 73.03% of controls (OR, 0.48;95% CI, 0.26-0.89;p value, 0.02). Conclusion: Our results indicate that longer CAG and GGN repeat may be associated with breast cancer whereas, the shorter GGN repeat length genotype of AR are protective.展开更多
The aim of this study was to examine whether CAG/GGN repeats are significant modulators of serum concentrations of total and free testosterone(T)as well as of luteinizing hormone(LH)in elderly men.Sixty-nine 60-to 80-...The aim of this study was to examine whether CAG/GGN repeats are significant modulators of serum concentrations of total and free testosterone(T)as well as of luteinizing hormone(LH)in elderly men.Sixty-nine 60-to 80-year-old men with subnormal T levels(≤11.0 nmol L^(-1))and 104 men with normal T levels taking part in a nested case-control study were used for these analyses.Sex hormones were measured and free T was calculated.The CAG and GGN polymorphisms in the androgen receptor gene were determined by polymerase chain reaction and subsequent direct sequencing.There were no differences in the CAG and GGN repeat lengths between the groups.In cross-sectional analyses of the whole cohort,total and free T were positively associated with CAG length(all P<0.05)before,but not after,waist circumference or body mass index was added to the model.CAG repeat lengths were weakly,but not independently,associated with total and free T.These findings indicate that when clinically evaluating T and LH levels in elderly men,the CAG and GGN repeat lengths do not need to be taken into consideration.展开更多
Androgen receptor (AR) gene has been extensively studied in diverse clinical conditions. In addition to the point mutations, trinucleotide repeat (CAG and GGN) length polymorphisms have been an additional subject ...Androgen receptor (AR) gene has been extensively studied in diverse clinical conditions. In addition to the point mutations, trinucleotide repeat (CAG and GGN) length polymorphisms have been an additional subject of interest and controversy among geneticists. The polymorphic variations in triplet repeats have been associated with a number of disorders, but at the same time contradictory findings have also been reported. Further, studies on the same disorder in different populations have generated different results. Therefore, combined analysis or review of the published studies has been of much value to extract information on the significance of variations in the gene in various clinical conditions. AR genetics has been reviewed extensively but until now review articles have focused on individual clinical categories such as androgen insensitivity, male infertility, prostate cancer, and so on. We have made the first effort to review most the aspects of AR genetics. The impact of androgens in various disorders and polymorphic variations in the AR gene is the main focus of this review. Additionally, the correlations observed in various studies have been discussed in the light of in vitro evidences available for the effect of AR gene variations on the action of androgens.展开更多
Aim: To investigate the role of CAG and GGN repeats as genetic background affecting androgen insensitivity syndrome (AIS) phenotype. Methods: We analyzed lengths of androgen receptor (AR)-CAG and GGN repeats in ...Aim: To investigate the role of CAG and GGN repeats as genetic background affecting androgen insensitivity syndrome (AIS) phenotype. Methods: We analyzed lengths of androgen receptor (AR)-CAG and GGN repeats in 69 AIS cases, along with 136 unrelated normal male individuals. The lengths of repeats were analyzed using polymerase chain reaction (PCR) amplification followed by allelic genotyping to determine allele length. Results: Our study revealed significantly shorter mean lengths of CAG repeats in patients (mean 18.25 repeats, range 14-26 repeats) in comparison to the controls (mean 22.57 repeats, range 12-39 repeats) (two-tailed P 〈 0.0001). GGN repeats, however, did not differ significantly between patients (mean 21.48 repeats) and controls (mean 21.21 repeats) (two- tailed P = 0.474). Among patients' groups, the mean number of CAG repeats in partial androgen insensitivity cases (mean 15.83 repeats) was significantly less than in complete androgen insensitivity cases (mean 19.46 repeats) (two- tailed P 〈 0.0001). Conclusion: The findings suggest that shorter lengths of repeats in the AR gene might act as low penetrance genetic background in varying manifestation of androgen insensitivity.展开更多
Spermatogenesis is an androgen-regulated process that depends on the action of androgen receptor (AR). Sperm production may be affected in men treated for testicular cancer (TC), and it is important to identify th...Spermatogenesis is an androgen-regulated process that depends on the action of androgen receptor (AR). Sperm production may be affected in men treated for testicular cancer (TC), and it is important to identify the factors influencing the timing of spermatogenesis recovery following cancer treatment. It is known that the CAG and GGN repeat numbers affect the activity of the AR; therefore, the aim of this study is to investigate if the CAG and GGN polymorphisms in the AR gene predict recovery of sperm production after TC treatment. TC patients (n = 130) delivered ejaculates at the following time points: postorchiectomy and at 6, 12, 24, 36, and 60 months posttherapy (TO, T6, T12, T24, T36, and T60). The CAG lengths were categorized into three groups, 〈22 CAG, 22-23 CAG, and 〉23 CAG, and the GGN tracts were also categorized into three groups, 〈23 GGN, 23 GGN, and 〉23 GGN. At T12, men with 22-23 CAG presented with a statistically significantly (P = 0.045) lower sperm concentration than those with other CAG numbers (8.4 × 10^6 ml^-1 vs 16 × 10^6 ml^-1; 95% CI: 1.01-2.65). This association was robust to omitting adjustment for treatment type and sperm concentration at TO (P= 0.021; 3.7× 10^6 ml^-1 vs 10 × 10^6 ml^-1; 95% CI: 1.13-4.90). The same trends were observed for total sperm number. The least active AR variant seems to be associated with a more rapid recovery of spermatogenesis. This finding adds to our understanding of the biology of postcancer therapy recovery of fertility in males and has clinical implications.展开更多
AIM: To systematically assess the association between sex hormone-binding globulin(SHBG)(TAAAA)n and androgen receptor(AR)(CAG)n polymorphisms and polycystic ovarian syndrome(PCOS) risk.METHODS: We searched MEDLINE(Pu...AIM: To systematically assess the association between sex hormone-binding globulin(SHBG)(TAAAA)n and androgen receptor(AR)(CAG)n polymorphisms and polycystic ovarian syndrome(PCOS) risk.METHODS: We searched MEDLINE(PubM ed), EMBASE and Web of Science database from inception to May2014. To avoid missing any additional studies, we looked through all the references of relevant articles. Case-control studies concerning the(CAG)n variants in the AR gene or the(TAAAA)n polymorphism in the SHBG gene in PCOS patients were included. Five studies regarding the(TAAAA)n polymorphism in the SHBG gene and 14 studies regarding the(CAG)n polymorphism in the AR gene met our criteria. Odd ratio(OR) and weighted mean difference(WMD) were selected as the effect size measurements to evaluate the influence of the(TAAAA)n polymorphism and(CAG)n variants on PCOS risk. Begg's test was used for the evaluation of publication bias.RESULTS: With respect to the relationship between the(TAAAA)n polymorphism and PCOS risk, the statistical results showed that there was no significant difference between PCOS patients and controls in the alleles of TAAAA(S: OR = 0.91, 95%CI: 0.78-1.05; L: OR = 1.10, 95%CI: 0.95-1.27). Subgroup analyses of the combination of alleles indicated similar results(shortshort: OR = 0.87, 95%CI: 0.66-1.14; short-long: OR = 1.12, 95%CI: 0.86-1.46; long-long: OR = 1.03, 95%CI: 0.72-1.47). As for the relationship between the(CAG)n polymorphism and PCOS risk, we found no association between CAG repeat variants and PCOS risk(WDM = 0.03, 95%CI:-0.13-0.08). Subgroup analyses by race and diagnosis criteria indicated the same results(Asian: WMD =-0.03, 95%CI:-0.14-0.07; Caucasian: WMD =-0.02, 95%CI:-0.24-0.21; the criteria of Rotterdam: WMD = 0.01, 95%CI:-0.01-0.03). CONCLUSION: There is no association between(TAAAA)n polymorphism in SHBG gene,(CAG)n repeat variants in AR gene and PCOS.展开更多
Objective: To study the relationship between the polymorphic (CAG)n micro-satellite of human androgen receptor (hAR) gene and prostate cancer (PCa). Methods: The number of (CAG)n repeats in 107 normal males were measu...Objective: To study the relationship between the polymorphic (CAG)n micro-satellite of human androgen receptor (hAR) gene and prostate cancer (PCa). Methods: The number of (CAG)n repeats in 107 normal males were measured by a two-step [α-32P]-dCTP incorporated asymmetric polymeric chain reaction (PCR), and the (CAG)n repeats of both malignant and nonmalignant prostate cells in fixed paraffin-embedded tissue (PET) specimen from 36 case of PCa were determined by sequence analysis. Results: The repeats of polymorphic (CAG) n among normal men ranged from 11 to 29, and the most frequent repeat was 22(18. 69%), with 23(14. 02%), 24(10. 28%) and 21(10. 28%) being less frequent. The (CAG)n repeats of malignant prostate cells equaled to that of nonmalignant adjacent prostate tissue cells from the same PET specimen in all 36 PCa, and the (CAG)n repeats in 36 PCa which ranged from 16 to 22 were shorter than that in normal males significantly (P<0. 05), while no significant difference in (CAG)n repeats among various grade of tumor's differentiation (well-differentiated, intermediate-differentiated and poor-differentiated) was found (P>0. 05). Conclusion; The present study suggest that short hAR gene (CAG)n micro-satellite might be associated with the occurrence of PCa, but not with the differentiation of PCa.展开更多
Background: Androgen insensitivity syndrome(AIS), a disorder of sexual development in 46, XY individuals, is caused by loss-of-function mutations in the androgen receptor(AR) gene. A variety of tumors have been report...Background: Androgen insensitivity syndrome(AIS), a disorder of sexual development in 46, XY individuals, is caused by loss-of-function mutations in the androgen receptor(AR) gene. A variety of tumors have been reported in association with AIS, but no cases with colorectal cancer(CRC) have been described.Case presentation: Here, we present a male patient with AIS who developed multiple early-onset CRCs and his pedigree. His first cousin was diagnosed with AIS and harbored the same AR gene mutation, but with no signs of CRC. The difference in clinical management for the two patients was that testosterone treatment was given to the proband for a much longer time compared with the cousin. The CRC family history was negative, and no germline mutations in well-known CRC-related genes were identified. A single nucleotide polymorphism array revealed a microduplication on chromosome 22q11.22 that encompassed a micro RNA potentially related to CRC pathogenesis. In the proband, whole exome sequencing identified a polymorphism in an oncogene and 13 rare loss-of-function variants, of which two were in CRC-related genes and four were in genes associated with other human cancers.Conclusions: By pathway analysis, all inherited germline genetic events were connected in a unique network whose alteration in the proband, together with continuous testosterone stimulation, may have played a role in CRC pathogenesis.展开更多
文摘This study aimed to investigate the correlations among androgen receptor (AR) CAG repeat polymorphism, sex hormones and penile length in healthy Chinese young adult men. Two hundred and fifty-three healthy men (aged 22.8 ± 3.1years) were enrolled. The individuals were grouped as CAG short (CAGs) if they harbored repeat length of 〈20 or as CAG long (CAGL) if their CAG repeat length was 〉20. Body height/weight, penile length and other parameters were examined and recorded by the specified physicians; CAG repeat polymorphism was determined by the polymerase chain reaction (PCR) method; and the serum levels of the sex hormones were detected by radioimmunoassay. Student's t-test or linear regression analysis was used to assess the associations among AR CAG repeat polymorphism, sex hormones and penile length. This investigation showed that the serum total testosterone (T) level was positively associated with the AR CAG repeat length (P = 0.01); whereas, no significant correlation of T or AR CAG repeat polymorphism with the penile length was found (P = 0.593). Interestingly, an inverse association was observed between serum prolactin (PRL) levels and penile length by linear regression analyses (β = -0.024, P = 0.039, 95% confidence interval (CI): -0.047, 0). Collectively, this study provides the first evidence that serum PRL, but not T or AR CAG repeat polymorphism, is correlated with penile length in the Han adult population from northwestern China.
基金supported by special fund for provincial science and technology cooperation project by Science and Technology Department of Henan province(122106000042)
文摘Objective:To explore the relation between the polymorphism of repetitive sequence in gene CAG of androgen receptor(AR)and the susceptibility and clinical stages as well as pathological grading of prostate cancer among Han population.Method:Sixty-eight cases with prostate cancer hospitalized in Urinary Surgery Department from Feb.2010 to Feb.2012 and 60 healthy cases were chosen as research subjects.Methods of PCR and direct sequencing were adopted to detect DNA sequence of AR gene and the length of repetitive sequence in CAG.Results:The lengths of repetitive sequence in CAG of patients with prostate cancer and healthy people were(22.3±4.6)and(23.0±4.9),respectively showing no statistical significance.Comparing length(repetitive sequence of CAG)>22,those with that<22 suffer a remarkably higher risk of prostate cancer(P<0.05).The number of repetitive sequence in CAG of patients at clinical stage C-D was less than that of patients at stage B,and the number of repetitive sequence in CAG of patients with poorly differentiated prostate cancer was also less than that of patients with moderately and highly differentiated prostate cancer.But there was no statistical significance int the difference(P>0.05);the proportion of patients with length<22 at clinical stage C-D was much larger than that of patients at clinical stage B(P<0.05),and as the aggravation of pathological grading,the proportion of patients with the length<22 was also remarkably increased and there was significant difference between patients with highly differentiated prostate cancer and those with poorly differentiated prostate cancer(P<0.05).Conclusions:There is correlation between the occurrence and development of prostate cancer in Han population and the polymorphism of repetitive sequence in gene CAG of androgen receptor.The less the number of repetitive sequence in CAG is,the higher the risk of prostate cancer will be and the more severe the clinical stage and pathological grading will be.
文摘Aim: The Androgen Receptor (AR) is a ligand-dependent transcriptional activator and the AR gene contains a highly polymorphic trinucleotide repeat CAG and GGN in the first exon. Given the lack of information AR-CAG and GGN repeat polymorphism and its potential correlation with breast cancer in South Indian women, we conducted a case-control study to observe the effects of CAG & GGN repeat length polymorphism and risk of breast cancer. Methods: Polymorphisms for AR-CAG and GGN repeat length was detected by Gene Scan analysis in the genomic DNA from cases with breast cancer and controls. Results: Association between AR genotype was calculated by categorising alleles as short (S) and long (L) and taking median value as the cut-off. LL genotype of CAG repeat was found to be associated with breast cancer (OR, 4.58;95% CI, 10.61-1.98;p—0.0004). GGN repeat having ≥21 was found in most of the cases and none of the cases showed 20 repeats thus indicate that alleles having homozygous repeat 20 may be protective towards breast cancer. Also, SS genotype was observed in 56.84% of cases and in 73.03% of controls (OR, 0.48;95% CI, 0.26-0.89;p value, 0.02). Conclusion: Our results indicate that longer CAG and GGN repeat may be associated with breast cancer whereas, the shorter GGN repeat length genotype of AR are protective.
基金the Swedish Research Council(Grant Nos.521-2004-6072 and K2005-72X-14545-03A)the Swedish Cancer Society(Grant Nos.4857-B05-03XCC,070482 and 070139)the Gunnar Nilsson Cancer Fund and the Center for Research in the Elderly in Tromsø,Norway.
文摘The aim of this study was to examine whether CAG/GGN repeats are significant modulators of serum concentrations of total and free testosterone(T)as well as of luteinizing hormone(LH)in elderly men.Sixty-nine 60-to 80-year-old men with subnormal T levels(≤11.0 nmol L^(-1))and 104 men with normal T levels taking part in a nested case-control study were used for these analyses.Sex hormones were measured and free T was calculated.The CAG and GGN polymorphisms in the androgen receptor gene were determined by polymerase chain reaction and subsequent direct sequencing.There were no differences in the CAG and GGN repeat lengths between the groups.In cross-sectional analyses of the whole cohort,total and free T were positively associated with CAG length(all P<0.05)before,but not after,waist circumference or body mass index was added to the model.CAG repeat lengths were weakly,but not independently,associated with total and free T.These findings indicate that when clinically evaluating T and LH levels in elderly men,the CAG and GGN repeat lengths do not need to be taken into consideration.
文摘Androgen receptor (AR) gene has been extensively studied in diverse clinical conditions. In addition to the point mutations, trinucleotide repeat (CAG and GGN) length polymorphisms have been an additional subject of interest and controversy among geneticists. The polymorphic variations in triplet repeats have been associated with a number of disorders, but at the same time contradictory findings have also been reported. Further, studies on the same disorder in different populations have generated different results. Therefore, combined analysis or review of the published studies has been of much value to extract information on the significance of variations in the gene in various clinical conditions. AR genetics has been reviewed extensively but until now review articles have focused on individual clinical categories such as androgen insensitivity, male infertility, prostate cancer, and so on. We have made the first effort to review most the aspects of AR genetics. The impact of androgens in various disorders and polymorphic variations in the AR gene is the main focus of this review. Additionally, the correlations observed in various studies have been discussed in the light of in vitro evidences available for the effect of AR gene variations on the action of androgens.
文摘Aim: To investigate the role of CAG and GGN repeats as genetic background affecting androgen insensitivity syndrome (AIS) phenotype. Methods: We analyzed lengths of androgen receptor (AR)-CAG and GGN repeats in 69 AIS cases, along with 136 unrelated normal male individuals. The lengths of repeats were analyzed using polymerase chain reaction (PCR) amplification followed by allelic genotyping to determine allele length. Results: Our study revealed significantly shorter mean lengths of CAG repeats in patients (mean 18.25 repeats, range 14-26 repeats) in comparison to the controls (mean 22.57 repeats, range 12-39 repeats) (two-tailed P 〈 0.0001). GGN repeats, however, did not differ significantly between patients (mean 21.48 repeats) and controls (mean 21.21 repeats) (two- tailed P = 0.474). Among patients' groups, the mean number of CAG repeats in partial androgen insensitivity cases (mean 15.83 repeats) was significantly less than in complete androgen insensitivity cases (mean 19.46 repeats) (two- tailed P 〈 0.0001). Conclusion: The findings suggest that shorter lengths of repeats in the AR gene might act as low penetrance genetic background in varying manifestation of androgen insensitivity.
文摘Spermatogenesis is an androgen-regulated process that depends on the action of androgen receptor (AR). Sperm production may be affected in men treated for testicular cancer (TC), and it is important to identify the factors influencing the timing of spermatogenesis recovery following cancer treatment. It is known that the CAG and GGN repeat numbers affect the activity of the AR; therefore, the aim of this study is to investigate if the CAG and GGN polymorphisms in the AR gene predict recovery of sperm production after TC treatment. TC patients (n = 130) delivered ejaculates at the following time points: postorchiectomy and at 6, 12, 24, 36, and 60 months posttherapy (TO, T6, T12, T24, T36, and T60). The CAG lengths were categorized into three groups, 〈22 CAG, 22-23 CAG, and 〉23 CAG, and the GGN tracts were also categorized into three groups, 〈23 GGN, 23 GGN, and 〉23 GGN. At T12, men with 22-23 CAG presented with a statistically significantly (P = 0.045) lower sperm concentration than those with other CAG numbers (8.4 × 10^6 ml^-1 vs 16 × 10^6 ml^-1; 95% CI: 1.01-2.65). This association was robust to omitting adjustment for treatment type and sperm concentration at TO (P= 0.021; 3.7× 10^6 ml^-1 vs 10 × 10^6 ml^-1; 95% CI: 1.13-4.90). The same trends were observed for total sperm number. The least active AR variant seems to be associated with a more rapid recovery of spermatogenesis. This finding adds to our understanding of the biology of postcancer therapy recovery of fertility in males and has clinical implications.
文摘AIM: To systematically assess the association between sex hormone-binding globulin(SHBG)(TAAAA)n and androgen receptor(AR)(CAG)n polymorphisms and polycystic ovarian syndrome(PCOS) risk.METHODS: We searched MEDLINE(PubM ed), EMBASE and Web of Science database from inception to May2014. To avoid missing any additional studies, we looked through all the references of relevant articles. Case-control studies concerning the(CAG)n variants in the AR gene or the(TAAAA)n polymorphism in the SHBG gene in PCOS patients were included. Five studies regarding the(TAAAA)n polymorphism in the SHBG gene and 14 studies regarding the(CAG)n polymorphism in the AR gene met our criteria. Odd ratio(OR) and weighted mean difference(WMD) were selected as the effect size measurements to evaluate the influence of the(TAAAA)n polymorphism and(CAG)n variants on PCOS risk. Begg's test was used for the evaluation of publication bias.RESULTS: With respect to the relationship between the(TAAAA)n polymorphism and PCOS risk, the statistical results showed that there was no significant difference between PCOS patients and controls in the alleles of TAAAA(S: OR = 0.91, 95%CI: 0.78-1.05; L: OR = 1.10, 95%CI: 0.95-1.27). Subgroup analyses of the combination of alleles indicated similar results(shortshort: OR = 0.87, 95%CI: 0.66-1.14; short-long: OR = 1.12, 95%CI: 0.86-1.46; long-long: OR = 1.03, 95%CI: 0.72-1.47). As for the relationship between the(CAG)n polymorphism and PCOS risk, we found no association between CAG repeat variants and PCOS risk(WDM = 0.03, 95%CI:-0.13-0.08). Subgroup analyses by race and diagnosis criteria indicated the same results(Asian: WMD =-0.03, 95%CI:-0.14-0.07; Caucasian: WMD =-0.02, 95%CI:-0.24-0.21; the criteria of Rotterdam: WMD = 0.01, 95%CI:-0.01-0.03). CONCLUSION: There is no association between(TAAAA)n polymorphism in SHBG gene,(CAG)n repeat variants in AR gene and PCOS.
基金Supported by the National Natural Science Foundation of China (No. 39670300)
文摘Objective: To study the relationship between the polymorphic (CAG)n micro-satellite of human androgen receptor (hAR) gene and prostate cancer (PCa). Methods: The number of (CAG)n repeats in 107 normal males were measured by a two-step [α-32P]-dCTP incorporated asymmetric polymeric chain reaction (PCR), and the (CAG)n repeats of both malignant and nonmalignant prostate cells in fixed paraffin-embedded tissue (PET) specimen from 36 case of PCa were determined by sequence analysis. Results: The repeats of polymorphic (CAG) n among normal men ranged from 11 to 29, and the most frequent repeat was 22(18. 69%), with 23(14. 02%), 24(10. 28%) and 21(10. 28%) being less frequent. The (CAG)n repeats of malignant prostate cells equaled to that of nonmalignant adjacent prostate tissue cells from the same PET specimen in all 36 PCa, and the (CAG)n repeats in 36 PCa which ranged from 16 to 22 were shorter than that in normal males significantly (P<0. 05), while no significant difference in (CAG)n repeats among various grade of tumor's differentiation (well-differentiated, intermediate-differentiated and poor-differentiated) was found (P>0. 05). Conclusion; The present study suggest that short hAR gene (CAG)n micro-satellite might be associated with the occurrence of PCa, but not with the differentiation of PCa.
基金supported in part by funds obtained through an Italian law that allows taxpayers to allocate 0.5 percent share of their income tax contribution to a research institution of their choice
文摘Background: Androgen insensitivity syndrome(AIS), a disorder of sexual development in 46, XY individuals, is caused by loss-of-function mutations in the androgen receptor(AR) gene. A variety of tumors have been reported in association with AIS, but no cases with colorectal cancer(CRC) have been described.Case presentation: Here, we present a male patient with AIS who developed multiple early-onset CRCs and his pedigree. His first cousin was diagnosed with AIS and harbored the same AR gene mutation, but with no signs of CRC. The difference in clinical management for the two patients was that testosterone treatment was given to the proband for a much longer time compared with the cousin. The CRC family history was negative, and no germline mutations in well-known CRC-related genes were identified. A single nucleotide polymorphism array revealed a microduplication on chromosome 22q11.22 that encompassed a micro RNA potentially related to CRC pathogenesis. In the proband, whole exome sequencing identified a polymorphism in an oncogene and 13 rare loss-of-function variants, of which two were in CRC-related genes and four were in genes associated with other human cancers.Conclusions: By pathway analysis, all inherited germline genetic events were connected in a unique network whose alteration in the proband, together with continuous testosterone stimulation, may have played a role in CRC pathogenesis.