A TA repeat polymorphism in the estrogen receptor gene is associated with osteoporotic fractures but polymorphisms in the first exon and intron are not.

Estrogen and the estrogen receptor (ER) play a central role in bone metabolism as illustrated by the loss of bone mass after menopause and the osteopenia in individuals with defect aromatase or ER. We therefore wanted to investigate the effect of polymorphisms in the ER-alpha gene on bone mass, bone turnover, and the prevalence of osteoporotic fractures in a study of 160 women and 30 men with vertebral fractures and 124 women and 64 men who are normal. Three previously described polymorphisms, G261-C in exon 1 and T-C and A-G in intron 1, in the ER gene were determined by restriction fragment length polymorphism (RFLP) using BstUI, Pvu II, and Xba I after polymerase chain reaction (PCR). A TA repeat polymorphism in the promoter region was examined by PCR and electrophoresis. The distribution of BstUI, Pvu II, and Xba I RFLPs was similar in the osteoporotic patients and the normal controls. No significant differences could be shown in bone mass or bone turnover between the genotypes. The mean number of TA repeats was lower in patients with osteoporotic fractures, 17.3+/-2.8 versus 18.6+/-2.8 in the normal controls (p < 0.01). This also was reflected in a significantly increased odds ratio of osteoporotic fractures in individuals with 11-18 repeats of 2.64 (95% CIs, 1.61-4.34). Furthermore, bone mineral density (BMD) of the lumbar spine was lower in individuals with low mean number of repeats than in individuals with high mean number of repeats (0.790+/-0.184 g/cm2 vs. 0.843+/-0.191 g/cm2; p < 0.05). This difference also was found in BMD of the total hip. Using multiple linear regression, mean number of TA repeats was a predictor of lumbar spine BMD (p < 0.05) and a BMD-independent predictor of fractures (p < 0.05). Mean number of TA repeats was not associated with levels of biochemical markers of bone turnover. All four polymorphisms were in linkage disequilibrium. A TA repeat polymorphism in the ER gene is associated with increased risk of osteoporotic fractures and a modest reduction in bone mass. Polymorphisms in the first exon and first intron of the ER gene are not associated with osteoporotic fractures, bone mass, or bone turnover.     

雄激素受体基因CAG多态性与迟发性性腺功能减退症的相关性研究

目的:研究雄激素受体基因(AR)重复序列(CAG)n多态性与迟发性性腺功能减退症(LOH)的关系,探讨LOH的发病机制。方法:共调查1 000例40～70岁中老年男性,其中19例迟发性性腺功能减退症患者,随机抽取127例正常健康中老年男性,测定甘油三酯(TG)、空腹血糖(FBG)、血清总睾酮(TT)、游离睾酮(fT),测量身高、体重、腰围(WC)、血压,并采用DNA测序方法进行AR基因外显子1氨基端转录调节区(CAG)n重复序列长度测定,比较两组各指标之间的差异。结果:(CAG)n重复次数为15～32(23.05±2.95)。正常健康中老年男性的体重指数(BMI)、FBG较LOH患者显著下降(P<0.01),而TG、TT及fT较LOH患者显著升高(P<0.01)。正常健康中老年男性AR基因(CAG)n重复数为22.54±3.06;LOH患者AR基因(CAG)n重复数为23.23±2.24;LOH患者(CAG)n重复数略高于正常健康人群,但两者比较无统计学意义(P=0.946)。(CAG)n重复长度显示:长组(n≥22)AR基因(CAG)n在LOH组和正常健康中老年男性组的频率分别为73.68%和48.82%(P<0.05)。相关分析显示:TT、fT与(CAG)n重复序列无明显相关性(r=0.04和r=0.025,P>0.05)。结论:LOH男性AR基因(CAG)n重复序列呈现多态性,长(CAG)n重复多态可能是LOH发病的遗传因素,但仍需进一步扩大样本量证实。     

Androgen receptor CAG repeat length polymorphism in benign prostatic hyperplasia (BPH): correlation with adenoma growth.

BACKGROUND: The androgen receptor (AR) gene has a polymorphic CAG microsatellite encoding variable-length glutamine repeats in the AR protein. The purpose of this study was to evaluate the association between the growth of benign prostatic hyperplasia (BPH) and the AR gene CAG repeat length. METHODS: We determined CAG repeat lengths in 176 BPH patients who underwent simple prostatectomy and in 41 control subjects without benign prostatic enlargement (non-BPE group). RESULTS: A statistically significant (P < 0.02) trend for large adenoma size with short CAG repeat length was found among the adenoma quartiles. CAG repeat length in the fourth quartile (large adenoma, 21.5 +/- 2.7) was significantly shorter than in the first quartile (small adenoma, 23.3 +/- 2.1, P < 0.02). It tended to be shorter than in the non-BPE group (23.1 +/- 2.4), but CAG repeat lengths in the entire BPH (22.4 +/- 2.5) and non-BPE groups did not significantly differ. The relative risk of large BPH (the fourth quartile) was 2.75 (95% confidence interval, 1.05-7.24; P < 0.05) on comparing CAG repeats of < or = 22-> or = 23. CONCLUSIONS: Shorter CAG alleles may be a genetic factor that promotes the growth of BPH.     

Polymorphisms in the transforming growth factor beta 1 gene and osteoporosis

Transforming growth factor (TGF)-beta1 is the most abundant growth factor in human bone. It is produced by osteoblasts and inhibits osteoclast proliferation and activity and stimulates proliferation and differentiation of preosteoblasts. Several polymorphisms have been described in the TGF-beta1 gene. Previously, we and others have found associations between some of these polymorphisms and bone mass. We therefore wanted to examine if these polymorphisms are also predictors of osteoporotic fractures. The polymorphisms G(-1639)-A, C(-1348)-T, C(-765)insC, T(29)-C, G(74)-C, 713-8delC, C(788)-T, and T(816-20)-C were examined using RFLP and sequencing in 296 osteoporotic patients with vertebral fractures and 330 normal individuals. Bone mineral density (BMD) was examined at the lumbar spine and at the femoral neck by DXA. Genotype distributions were in H-W equilibrium. Linkage disequilibrium was found between the polymorphisms. The T(816-20)-C genotypes were distributed differently among osteoporotic patients and normal controls. The TT genotype was less common in individuals with osteoporotic fractures (chi(2) = 6.02, P < 0.05). BMD was higher in individuals with the TT-genotype (T(816-20)-C) at the lumbar spine, 0.960 +/- 0.173 g/cm(2) compared with individuals with the TC or CC genotypes: 0.849 +/- 0.181 g/cm(2) and 0.876 +/- 0.179 g/cm(2), respectively (P < 0.001, ANOVA). Similar differences between genotypes were found at the different hip regions as well as at the total hip. Individuals with the TT-genotype (C(-1348)-T) had higher bone mass at the femoral neck: 0.743 +/- 0.134 g/cm(2) compared with 0.703 +/- 0.119 g/cm(2) in individuals with TC or CC genotypes (P < 0.05). Individuals with the CC-genotype (T(29)-C) had higher bone mass at the femoral neck, 0.735 +/- 0.128 g/cm(2) compared with 0.703 +/- 0.120 g/cm(2) in individuals with TC or TT genotypes (P < 0.05) and at the total hip: 0.852 +/- 0.166 g/cm(2) vs. 0.818 +/- 0.149 g/cm(2), respectively (P < 0.05). None of the other polymorphisms were distributed differently in patients and controls and did not affect BMD. In conclusion, The TT genotype of the T(816-20)-C polymorphism is less common in patients with osteoporotic fractures and is associated with higher bone mass both at the lumbar spine and at the hip. The C(-1348)-T and T(29)-C polymorphisms were distributed similarly in osteoporotic patients and normal controls, however, the rare genotypes were associated with higher bone mass at the hip.     

CAG repeat expansion in the androgen receptor gene is not associated with male infertility in Indian populations

CAG repeat expansion in exon 1 of the androgen receptor (AR) gene has been reported to be associated with male infertility in some but not all populations. Until now, studies have not been carried out to examine this among Indian populations. For the first time, we have analyzed the CAG repeat motif in the AR gene in 280 men with azoospermia and in 201 men with normal fertility. The mean number of CAG repeats in the AR gene of men with azoospermia was 21.7 +/- 0.18, with a high incidence of repeat number 22. Among fertile-control men, the mean number of CAG repeats was 22.4 +/- 0.19, with a predominance of repeat number 23. The highest number of CAG repeats (32) was found with low frequency in both fertile and azoospermic groups. Comparison of fertile men and those with azoospermia on the basis of CAG repeats revealed that the number of CAG repeats in both groups were similar, as revealed with a paired t test (t = 0.04; P =.967). Expansion of the CAG repeat in the AR gene is therefore not associated with male infertility in Indian populations. This suggests that what is true for one population may not be true for other populations.     

Polymorphisms in the CYP19 and AR Genes—Relation to Bone Mass and Longitudinal Bone Changes in Postmenopausal Women With or Without Hormone Replacement Therapy: The Danish Osteoporosis Prevention Study

Polymorphisms in the androgen receptor ( AR) gene and genes encoding enzymes involved in synthesis of sex steroids (e.g., the CYP19 gene encoding aromatase) have recently received attention in osteoporosis research. In the Danish Osteoporosis Prevention Study, recent postmenopausal women were allocated to either hormone replacement therapy (HRT) or no treatment. We genotyped 1792 women for the CYP19 (TTTA)(n) repeat [short (TTTA)(n 7)] the CYP19 C(1558)-T, and the AR (CAG)(n) repeat polymorphism [short (CAG)(n < 22), long (CAG)(n >or= 22)], and investigated associations with bone mineral density (BMD) and 5-year change in BMD. The CYP19 polymorphisms were in strong linkage disequilibrium. Perimenopausal bone mass or bone loss in untreated women was not associated with the CYP19 polymorphisms. In hormone-treated women, BMD increase in the femoral neck was highest (+0.3%/year) for long CYP19 alleles, lowest (-0.09%/year) for short alleles, and intermediate (-0.002%/year) in heterozygous women, P = 0.015. Differences were also significant in the lumbar spine, total hip, and ultradistal forearm. The C(1558)-T T-allele was associated with a more pronounced response to HRT ( P = 0.04, total hip). AR genotype was not related to BMD, but a modifying effect of sex hormone-binding globulin (SHBG) was present. In the highest SHBG quartile (SHBG > 95 nmol/1, n = 222), AR genotype was associated with baseline BMD (femoral neck: P < 0.001, total hip: P = 0.008), but without a clear gene dosage effect. We have demonstrated that polymorphisms in the CYP19 gene are associated with the magnitude of bone gain in response to HRT and that the (CAG)(n) repeat polymorphism in the AR gene is associated with bone mass in women with high levels of SHBG. These findings emphasize the complexity of the genetics of bone mass and bone loss.     

Echogenic Carotid Artery Plaques are Associated with Vertebral Fractures in Postmenopausal Women with Low Bone Mass

Although low bone mass has been associated with atherosclerosis even after adjustment for age, little is known about the association between vertebral fractures and calcified atherosclerotic plaques. Our objective was to investigate whether osteoporotic vertebral fractures are independently related to the prevalence of atherosclerotic carotid plaques in postmenopausal women with low bone mass. We enrolled 195 postmenopausal women with osteopenia or osteoporosis. Bone mineral density and the presence of vertebral fractures were assessed. Intima media thickness and atherosclerotic plaques of the carotid artery were assessed using ultrasonography. Of the 195 subjects in the study, 84 had no plaques and 111 had at least one. The percentage of women with vertebral fractures was significantly higher in subjects with echogenic carotid plaques than in those without (27% vs. 11%, respectively; P < 0.05). However, there was no difference in the prevalence of vertebral fractures between women with echolucent plaques and those without (10.9% vs. 10.7%, respectively; P = nonsignificant). By logistic regression analysis with multivariate adjustment, age (P < 0.01), dyslipidemia (P < 0.05), and the presence of vertebral fracture (P < 0.05) were independent risk factors for echogenic carotid plaques. Osteoporotic vertebral fractures are associated with an increased risk of echogenic atherosclerotic plaques in postmenopausal women with low bone mass. It appears that the high association of echogenic atherosclerotic plaques and vertebral fractures could partially explain why osteoporotic vertebral fractures are linked to increased mortality.     

绝经后妇女骨质疏松性椎体骨折与腰椎骨密度的关系

目的探讨绝经后妇女骨质疏松性椎体骨折与腰椎骨密度的关系。方法选择骨质疏松性椎体骨折的绝经后妇女23例为骨折组,无椎体骨折的25例绝经后骨质疏松妇女为对照组。两组的年龄、绝经年限、身高、体重、体重指数差异无显著性,均行胸腰椎正侧位X线摄片。用双能X线吸收仪（DXA）测量的腰椎（L2-4）前后位骨密度（BMD）、骨矿含量（BMC）和T值。结果骨折组BMD、BMC和T值均低于对照组（P〈0.01）。结论腰椎BMD降低与绝经后妇女的骨质疏松性椎体骨折相关。绝经后骨质疏松妇女应重视BMD变化,预防椎体骨折的发生。     

Ultrasound attenuation of the calcaneus: A sensitive and specific discriminator of osteopenia in postmenopausal women

Summary Recent studies have evaluated techniques for estimating bone mass without radiation. The present study compares broadband ultrasound attenuation of the calcaneus and bone densities of the femoral neck and the lumbar spine in 17 normal women and 41 women with osteoporosis. Twenty of the osteoporotic women had spine (n=16) or femoral neck (n=4) fractures. There was a significant decrease in the broadband ultrasound attenuation (P<0.001) in women with osteoporosis compared with normal women. The osteoporotic women also showed a decrease in vertebral (P<0.0001) and femoral neck (P<0.0001) densities compared with normal women. At 63 dB/MHz, the sensitivity and specificity of broadband ultrasound attenuation for decreased bone mineral density with or without fractures were 76%. All women with fractures had a broadband ultrasound attenuation less than 72 dB/MHz. This corresponded to a specificity of 41%. To determine whether broadband ultrasound attenuation correlated with trabecular bone volume, samples of cadaver calcaneus were analyzed. The histologic determination showed a significant correlation between broadband ultrasound attenuation and trabecular bone volume (r=0.992,P=0.008). These results suggest broadband ultrasound attenuation of the calcaneus reflects bone mass and can be used as a safe and sensitive indicator for decreased axial bone density.     

Androgen receptor gene polymorphisms and the fat-bone axis in young men and women

Androgen receptor (AR) CAG(n) (polyglutamine) and GGN(n) (polyglycine) repeat polymorphisms determine part of the androgenic effect and may influence adiposity. The association of fat mass, and its regional distribution, with the AR CAG(n) and GGN(n) polymorphisms was studied in 319 and 78 physically active nonsmoker men and women (mean ± SD: 28.3 ± 7.6 and 24.8 ± 6.2 years old, respectively). The length of CAG and GGN repeats was determined by polymerase chain reaction and fragment analysis, and confirmed by DNA sequencing of selected samples. Men were grouped as CAG short (CAG(S)) if harboring repeat lengths ≤ 21, the rest as CAG long (CAG(L)). The corresponding cutoff CAG number for women was 22. GGN was considered short (GGN(S)) if GGN ≤ 23, the rest as GGN long (GGN(L)). No association between AR polymorphisms and adiposity or the hormonal variables was observed in men. Neither was there a difference in the studied variables between men harboring CAG(L) + GGN(L),CAG(S) + GGN(S),CAG(S) + GGN(L), and CAG(L) + GGN(S) combinations. However, in women, GGN(n) was linearly related to the percentage of body fat (r = 0.30, P < .05), the percentage of fat in the trunk (r = 0.28, P < .05), serum leptin concentration (r = 0.40, P < .05), and serum osteocalcin concentration (r = 0.32, P < .05). In men, free testosterone was inversely associated with adiposity and serum leptin concentration, and positively with osteocalcin, even after accounting for differences in CAG(n), GGN(n), or both. In summary, this study shows that the AR repeat polymorphism has little influence on absolute and relative fat mass or its regional distribution in physically active men. In young women, GGN length is positively associated with adiposity, leptin, and osteocalcin.     

Ability of four different techniques of measuring bone mass to diagnose vertebral fractures in postmenopausal women

Since bone mass has been shown to be an important determining factor of fractures in vitro, we undertook a study to evaluate whether bone mass measurements could separate postmenopausal women with vertebral compression fractures from women of a similar age without fractures. We also wanted to see if methods of measuring bone mass at the spine would be more sensitive or specific than methods that measured bone at the wrist or the entire skeleton. The techniques used were: total body calcium by neutron activation analysis (TBC), single photon absorptiometry (SPA), dual photon absorptiometry (DPA), and quantitative computed tomography (QCT). Normal women aged 20-85 were measured, but only those greater than 50 yr were used in the analysis. Mean values for women with fractures were significantly lower than normals (p less than .001): TBC 642 +/- 103 g vs. 764 +/- 114; SPA .658 +/- .134 g/cm vs. .779 +/- .142; DPA 3.75 +/- .82 g/cm vs. 4.37 +/- .86; QCT 59.0 +/- 25.7 mg/cc vs. 92.6 +/- 36.0. However, each of the methods showed considerable overlap between women with and without fractures. At 90% specificity the sensitivities of the tests were: TBC 34%; SPA 29%; DPA 33%; QCT 36%. When values were expressed as the % expected (based on age and height) then the sensitivities were: TBC 52%; SPA 36%; DPA 35%; QCT 44%. Using Bayes' theorem, we constructed curves showing the posttest probability of these tests at a prevalence of 20%. None of these bone mass measuring techniques showed complete separation between normal and osteoporotic women with fractures; about one-half of the women with fractures were below the normal range. The risk of having a fracture increases as bone mass declines, but our data suggest that bone mass is not the only factor leading to vertebral fractures in postmenopausal women.     

Osteoporotic fractures are associated with an 86-base pair repeat polymorphism in the interleukin-1--receptor antagonist gene but not with polymorphisms in the interleukin-1beta gene.

Interleukin-1beta (IL-1beta) is a potent stimulator of bone resorption, and has been implicated in the pathogenesis of high bone turnover and osteoporosis. IL-1 receptor antagonist (IL-1ra) is a competitive inhibitor of IL-1beta effects and the biological effects of IL-1beta are therefore proportional to the ratio IL-1beta/IL-1ra. The coding regions of IL-1beta were examined for sequence variations by SSCP and sequencing after polymerase chain reaction (PCR) of genomic DNA. Three previously described polymorphisms (C(-511)-T, G(3877)-A and C(3954)-T) in the IL-1beta gene were determined by restriction fragment length polymorphism (RFLP) using Ava I, Aci I, and Taq I after PCR. The 86-base pair repeat polymorphism in IL-1ra was examined by PCR and electrophoresis and the T11100-C polymorphism in the IL-1ra gene was examined by RFLP using MspA1I after PCR. All polymorphisms were related to bone mass, biochemical markers of bone turnover, and presence of fracture in a study including 389 osteoporotic patients with vertebral fractures and normal controls. Two normal women were heterozygous for a shift from cytosine to thymine (C3263-T) in exon 4 of the IL-1beta gene. This substitution did not affect the amino acid sequence. We did not find other sequence variations in the IL-1beta gene apart from the already known polymorphisms. The distribution of C(-511)-T, G(3877)-A, and C(3954)-T genotypes was similar in the osteoporotic and the normal controls. No significant differences could be shown in bone mass or bone turnover. In the IL-1ra gene almost complete linkage was confirmed between the already known polymorphisms: G(1731)-A, G(1821)-A, A(1868)-G, G(1887)-C, T(8006)-C, C(8061)-T, 86 base pair variable number tandem repeat (VNTR), A(9589)-T, and a new polymorphism: T(1934)-C. The A1A1/A3 genotypes of the IL-1ra VNTR polymorphism were significantly more frequent in osteoporotic patients (56.2%) compared with age-matched normal controls (43.3%) (chi2 = 4.09; p = 0.043). The relative risk of osteoporotic fractures was increased to 1.68 (95% CI, 1.01-2.77) in individuals with A1A1/A3 genotypes. Bone mineral density (BMD) of the lumbar spine was reduced in individuals with A1A1/A3 genotypes (p = 0.014, analysis of variance [ANOVA]). The difference in bone mass between A1A1/A3 and A2A1/A2 tended to increase with increasing age. T1100-C genotypes were distributed similarly in osteoporotic patients and normal controls and the polymorphism was without effect on bone mass and biochemical markers of bone turnover. In conclusion, an 86-base pair repeat polymorphism in the IL-lra gene is associated with increased risk of osteoporotic fractures. Other polymorphisms in the IL-1ra and the IL-1beta genes are not associated with osteoporotic fractures or alterations in bone mass or bone turnover.     

Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism is associated with osteoporotic vertebral fractures, but is a weak predictor of BMD

Osteoporosis is a common disease with a strong genetic component. Linkage studies have suggested linkage between BMD and loci on chromosome 1. The MTHFR gene is located on chromosome 1. MTHFR catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methylenetetrahydrofolate, which is used for homocysteine methylation to methionine. The rare genotype (TT) of the C677T polymorphism has previously been demonstrated to be associated with increased plasma homocysteine levels in individuals with inadequate plasma folate levels. Recently, the TT genotype has been found to be associated with reduced bone mass. We therefore examined if the C677T polymorphism in the MTHFR gene is associated with changes in bone mass and risk of osteoporotic fractures in 388 osteoporotic patients and 336 normal individuals. The distributions of the genotypes CC, CT and TT in women with osteoporotic vertebral fractures and normal controls were 43.5%, 42.2% and 14.3% and 52.0%, 42.0% and 8.0%, respectively, ²=5.62, P=0.06. Since studies of the functionality of this polymorphism have revealed that only the TT genotype is associated with biochemical changes, we also compared the prevalence of the TT genotype versus the CT- and CC genotypes in patients and controls and found that the TT genotype is significantly more common in women with vertebral fractures (14.3%) compared with normal controls (8.0%), ²=4.31, P<0.05. Logistic regression analysis demonstrated that vertebral fractures were significantly associated with BMD (lumbar spine) and height but only marginally with the MTHFR genotype (P=0.06). Multiple linear regression analysis revealed that weight, age and the MTHFR polymorphism were predictors of lumbar spine BMD in women. However, age- and gender-corrected BMD of the lumbar spine and the hip was not significantly different between MTHFR genotypes. Furthermore, individuals with the TT genotype did not have BMD significantly lower than the combined group of individuals with the CT- or CC genotypes. In conclusion, we have demonstrated that the rare TT genotype of the C677T polymorphism in the MTHFR gene is associated with increased risk of osteoporotic fractures in women and a weak predictor of lumbar spine BMD.     

The association of androgen- and oestrogen-receptor gene polymorphisms with urolithiasis in men

OBJECTIVE: To evaluate the association of urolithiasis with polymorphic microsatellite (encoding cytosine, adenine, and guanine, CAG) repeats in the exon 1 region of the androgen receptor (AR) gene and thymine/adenine (TA) repeats in the oestrogen receptor (ER). PATIENTS AND METHODS: Patients with urolithiasis (149) and a group of normal controls (102) were examined and compared. The CAG repeats of the AR gene and TA repeats of the ER gene were detected by polymerase chain reaction. The CAG repeats ranged from 171 bp (10 CAG repeats with 141 bp of amplified flanking sequences) to 270 bp (43 CAG repeats). The TA repeats ranged from 160 bp to 194 bp. Associations between calcium oxalate stone disease and the CAG repeats in AR gene and TA repeats in ER gene were then evaluated. The results were classified according to sex and peaks in allelic frequency distribution. RESULTS: There was a significant difference between the male stone patients and the normal controls in the distribution of CAG repeats in the AR gene. Both groups showed a high percentage of 21-repeats in the allelic distribution, at 17 (16%) and 20 (37%) in stone patients and normal controls, respectively. The results indicate that 21-CAG repeats might be related to a lower risk of stone formation in men (P < 0.05). In the ER gene, the peak allelic distribution of TA repeats was 14, showing a significant difference between male stone patients and the normal control subjects (P < 0.01). There were no statistical differences between female stone patients and the control subjects in either the AR or the ER gene. CONCLUSION: Urolithiasis among men appears to be associated with AR gene CAG repeat and ER gene TA repeat polymorphisms, whereas there was no significant association among female stone patients. These sex hormone receptors seem to be related to the higher incidence of stone formation among men.     

唑来膦酸治疗老年女性骨质疏松性椎体压缩性骨折效果观察

目的观察唑来膦酸辅助治疗女性骨质疏松性椎体压缩性骨折效果。方法 126例老年压缩性骨折女性患者随机分为对照组和治疗组。两组患者均进行给予PVP治疗,治疗组给予唑来膦酸5 mg治疗。治疗前及治疗12个月后使用视觉模拟疼痛评分(VAS)及Oswestry功能障碍指数评分(ODI)评价患者疼痛改善情况;治疗前及治疗12个月检测患者骨密度改变情况和骨代谢指标:骨钙素(BGP)和I型前胶原肽(CTX)水平的变化。结果治疗后12个月,两组患者VAS与ODI评分较治疗前均有显著改善(P0.05),且治疗组患者上述评分改善情况较对照组更为明显(P0.05)。治疗后12个月,治疗组骨密度较治疗前明显升高(P0.05),血清CTX较治疗前明显降低(P0.05),和对照组比较差异有统计学意义(P0.05);而治疗前后BGP无明显改变(P0.05),对照组上诉指标治疗前后比较,差异无统计学意义(P0.05)。结论唑来膦酸有助于改善老年骨质疏松椎体压缩性骨折术后骨密度和骨代谢,降低VAS与ODI评分,值得临床推广。     

Androgen receptor gene CAG repeat polymorphism and breast cancer risk in Iranian women: a case-control study

We investigated the association between polymorphic expansion of trinucleotide CAG repeats in androgen receptor (AR) gene and breast cancer risk among Iranian women in a matched case-control study. There was a strong overall association between per CAG repeat increments in average repeat length and the risk of the malignancy [OR=3.56; 95% CI, 2.80-5.29]. Women carrying one or two alleles with [CAG]n repeat ≥22 units were at increased risk of breast cancer [OR=2.03; 95% CI, 1.56-2.6]. The risk was significantly increased in homozygous longer repeats, versus homozygous alleles <22. We observed reduced risk of developing the tumor in positive familial breast cancer subjects carrying repeats ≥22 and 23. Homozygosity for the longer [CAG]n repeats may be linked to the increased breast cancer risk. In contrast to previous reports, longer AR [CAG]n repeat alleles may decline the risk among women with a familial breast cancer.     

雄激素受体基因CAG多态性对男性激素避孕有效性影响的研究

目的:分析应用肌注十一酸睾酮酯(TU)进行激素避孕的男性志愿者中起反应者与不起反应者雄激素受体(AR)基因(CAG)n微卫星多态性,并探讨该多态性对激素避孕效果的影响。方法:29例TU不起反应者和34例起反应者分别作为试验组和对照组,应用PCR和DNA测序技术对两组外周血标本进行CAG重复数测定,分析该微卫星多态性对激素避孕效果的影响。结果:试验组和对照组CAG重复数的均数分别为23.62和22.97,均数比较差异无显著性(P>0.05)。短组CAG(n≤22)在试验组和对照组的分布分别为51.7%、50.0%;长组CAG(n>22)在试验组和对照组分布分别为48.3%、50.0%,长短组分布相同。CAG重复数与精子密度之间未见相关性。在FSH浓度>0.2IU/L组中,CAG重复数>22的受试者达到无精子症的机会是其他受试者的1.5倍。结论:受试者AR基因(CAG)n重复数呈多态性,但不反应组与反应组之间不具有显著性差异,AR基因CAG重复数或其他因素与男性激素避孕效果之间的关系有待进一步探讨。     

Interpretation of lumbar spine densitometry in women with fractures

Identification of postmenopausal women at risk of developing osteoporotic fractures is a major clinical problem. In this study the use of projected planar lumbar bone density values for individual fracture risk assessment was questioned. Osteodensitometry (DXA) results from 415 normal women, 62 women with previous vertebral compressions, and 76 women with previous low-energy fractures were analyzed, together with their body size and lumbar vertebral body size variables. The following were found: (1) Lumbar vertebral projected bone mineral areal density (BMD) and bone mineral content (BMC) of normal women correlated with body size variables (p<0.001). (2) Lumbar vertebral body size variables also correlated with body size variables (p<0.001). Logistic regression analysis of measured and derived physical variables from women without and with vertebral compression fractures (n=477) showed: (3) The best compression fracture discriminator, significantly better than BMD, was BMC divided by (H_max/165 cm)¹⁵×(D/4.35 cm)^1.5, where H_max is the body height (cm) at the menopause, and D the mean lumbar vertebral diameter of the three mid-lumbar vertebral bodies (cm). This parameter was termed BMC_corr.. ROC analysis showed: (4) At a BMC_coor. true positive ratio of 80% the corresponding uncorrected BMC or BMD true positive ratio was only 60%. The corresponding false positive ratio was 6%. Lumbar osteodensitometry could not be used to identify women with a history of peripheral low-energy fractures. (5) BMC_coor. did not, unlike BMC and BMD, correlate with body size and vertebral size variables. (6) Likewise, an observed correlation between BMC and lean body mass in a subpopulation of 116 normal women was abolished when BMC_corr. replaced BMC. We suggest that vertebral compression fracture risk limits based on BMC, corrected for individual differences in body size and vertebral body size, replace the commonly used BMD fracture risk limits. The discriminatory ability of BMC_corr. for low-energy fractures needs to be tested in a different population.This investigation was carried out as part of a collaborative study by the Danish Osteoporosis Study Group (DOPS: O. Helmer Sørensen, L. Mosekilde, P. Charles, H. Beck-Nielsen and S. Pors Nielsen).     

CAG repeat length in androgen receptor gene and male infertility in Egyptian patients

The CAG repeat and its association with infertility has been debatable. Therefore, this study was planned to assess the distribution of CAG repeat expansion in Egyptian patients and to investigate its association with male infertility. Forty-five infertile men were eligible for the study in addition to 20 aged-matched fertile males as control. Semen analysis, scrotal sonography, assay of serum testosterone, follicle-stimulating hormone (FSH) and luteinising hormone (LH), and determination of the CAG repeat number within exon 1 of the androgen receptor (AR) gene were carried out. Statistically significant difference was found between infertile and control groups regarding sperm count, sperm motility, serum FSH level and CAG repeats (P < 0.05); statistically insignificant difference for the CAG repeats (P = 1.0) was found between oligozoospermic and asthenospermic groups; negative correlation was found between CAG repeat length and sperm count, and a positive correlation was found between CAG repeat length and serum FSH (P < 0.05). Our results validate the concept that long stretches of CAG repeat may be associated with lower AR function with derangement of sperm production, and this may contribute to male infertility in Egyptian men.