雄激素受体基因CAG、GGN重复片段多态性与指长比(2D∶4D)的关联性

目的探讨雄激素受体(AR)基因CAG、GGN重复片段多态性与指长比之间的关联性。方法研究对象来自宁夏医科大学2011级健康学生共685例,男性294例,平均年龄(20.02±1.28)岁,女性391例,平均年龄(19.25±1.55)岁。用ABI 3730XL测序仪测定AR基因的(CAG)n及(GGN)n重复数目,照片打好点后用电子游标卡尺对指长比进行测定。2D∶4D经均值±2标准差筛选,用独立样本t检验检测2D∶4D在男性与女性个体中的分布差异。用四分位法筛选出较低(Q1)与较高(Q3)2D∶4D。用相关分析检验AR基因中CAG和GGN两个多态性位点与2D∶4D的关联性。结果女性右手、左手及左右手平均2D∶4D均高于男性(P0.05,P0.01,P0.01),但DR-L2D∶4D的分布差异无统计学意义(P0.05)。AR CAG/GGN重复多态性与男性右手及左手2D∶4D无关联性(P0.05),但CAG重复多态性与Q1 DR-L及Q3平均2D∶4D存在关联性(r=0.280,P0.05,r=0.274,P0.05)。女性较短CAG等位基因与Q3平均2D∶4D存在关联性(r=0.337,P0.05),女性较长CAG等位基因与Q3右手及DR-L2D∶4D存在关联性(r=0.238,P0.05;r=0.175,P0.05),女性平均CAG等位基因与Q3平均2D∶4D存在关联性(r=0.236,P0.05)。女性较长GGN等位基因与女性右手2D∶4D存在关联性(r=0.204,P0.05),女性平均GGN等位基因与Q3平均2D∶4D存在关联性(r=0.225,P0.05)。结论 AR基因CAG与GGN重复片段多态性可能与指长比存在关联性,联合运用四分位法与相关分析可能是揭示AR多态性与指长比关联性的一种更好的方法。     

宁夏回、汉族群体雄激素受体基因(CAG)n、(GGN)n重复多态性研究

目的 研究雄激素受体(androgen receptor,AR)基因(CAG)n、(GGN)n重复序列多态性在宁夏回、汉族群体中的分布特征.方法 用ABI 3730XL测序仪测定AR基因的(CAG)n及(GGN)n重复数目并对结果进行分析.结果 CAG等位基因在宁夏回、汉族群体中的分布差异无统计学意义(P＞0.05).GGN等位基因在两个群体中的分布差异有统计学意义(P＜0.01),汉族女性GGN重复数为23的等位基因频率(48.4％)显著低于回族女性(64.7％,P=0.01).结论 AR基因GGN等位基因在宁夏回、汉族群体中的分布差异有统计学意义(P＜0.01).     

维吾尔族前列腺癌与雄激素受体CAG重复多态性的关系

目的　探讨雄激素受体 (androgenreceptor ,AR )基因CAG重复长度与维吾尔族前列腺癌(prostatecancer ,PC)危险性及临床表现的关系。方法　应用PCR和直接测序的方法对维吾尔族 3 1例PC和 80名健康老年男性患者外周血标本进行AR基因CAG重复长度测定。结果　PC和对照组AR基因CAG重复长度平均为 2 2 .3和 2 2 .8,范围为 13 3 0 ,两者比较差异无显著性 (P =0 .5 72 )。AR基因CAG重复长度 <2 2与≥ 2 2比较 ,OR值为 2 .3 2 ( 95 %可信区间为 1.0 0 5 .46,P =0 .0 5 ) ,AR基因CAG重复长度与PC发病年龄 (相关系数 0 .2 0 1,P =0 .2 8)、前列腺特异抗原 (相关系数 -0 .0 92 ,P =0 .62 )无相关性 ,与前列腺癌分级也无关 (P >0 .0 5 )。结论　短的AR基因CAG重复长度与维吾尔族前列腺癌的危险性有关 ,而与前列腺癌的发病年龄、PSA水平及病理分级无关。     

中国男性雄激素受体基因(CAG)n重复多态性的初步研究

目的 研究正常中国男性雄激素受体（androgen receptor,AR)基因（CAG）n重复序列的多态性。方法 应用DNA测序基础上的[α-^32P]dCTP掺入不对称PCR-变性聚丙烯酰胺凝胶电泳（Polyacrylamide gel electrophoresis,PAGE)方法,对107名正常男性AR基因的（CAG）n重复数进行测定。结果 AR基因（CAG）n序列在正常男性人群中呈现重复多态性,其重复范围为11-29,集中于20-24,以22最多。结论 AR基因（CAG）n序列在正常男性人群中呈现重复多态性,为今后进一步研究其病理学及遗传学意义打下基础。     

男性不育症患者X染色体雄激素受体基因外显子1、3、4状态筛选研究

目的研究雄激素受体（androgen receptor,AR）基因与特发无精症之间的关系。方法运用分子生物学方法分别检测35名无精症患者和20名对照组正常男性雄激素受体基因的3个功能区的DNA片段,结果实验组患者和正常男性AR外显子1中（CAG）n重复数在11~27之间,两组无显著差别,35例无精症患者用PCR扩增出雄激素受体外显子3（exon3）片段35例（100%）和外显子4（exon4）片段34例（97.15%）,20名正常已生育男性扩增出AR外显子3（exon3）片段20例（100%）和外显子4（exon4）片段20例（100%）。结论（CAG）n基因多态性与男性精子生成障碍无相关性,exon4缺失通过影响靶细胞核的类固醇激素-受体结合物数量在精子发生中的作用需进一步探讨。     

白介素4受体基因Q576R多态性及与变应性鼻炎的相关性

目的对变应性鼻炎患者行白介素4受体基因Q576R分型,探讨白介素4受体基因Q576R基因与变应性鼻炎遗传易感性的相关性。方法用PCR-RFLP法为69名无亲缘关系的变应性鼻炎患者和91名无血缘关系的健康汉族人行白介素4受体基因Q576R分型。结果AR组中TIgE含量明显高于对照组。(P<0.001),Q576R各基因型之间TIgE无显著性差异,在AR组中QR基因型频率高于对照组(P=0.007),QQ基因型频率低于对照组(P=0.02)。AR组与对照组之间等位基因频率存在显著性差异(P=0.005),AR组的R等位基因频率高于对照组(OR=2.18)。结论Q576R基因多态性与AR存在相关性,R等位基因可能是AR的易感基因。     

云南汉族人群HLA-B基因多态性与类风湿性关节炎的相关性研究

目的 探讨HLA-B基因多态性与类风湿性关节炎(rheumatoid arthritis,RA)的关联性.方法 采用DNA测序和序列特异性引物聚合酶链式反应(polymerase chain reaction-sequencespecific primer,PCR-SSP)方法检测云南汉族中271例类风湿性关节炎患者和264例正常人群的HLA-B基因多态性并进行关联性分析.结果 女性类风湿性关节炎患者的HLA-B*40基因频率(8.84％)明显低于女性对照组(18.33％)(P=0.000),HLA-B*51基因频率(9.53％)明显高于对照组(2.83％)(P=0.000),HLA-B*48基因频率(0.23％)明显低于对照组(2.33％)(P=0.007),差异均有统计学意义.HLA-B*40、HLA-B*51、HLA-B* 48的基因频率在男性类风湿性关节炎患者和男性对照中的分布无统计学差异(P值分别为0.535、0.691、0.289).结论 云南汉族人群中HLA-B基因分布存在多态性.HLA-B基因多态性与云南汉族人群女性类风湿性关节炎的发病相关,HLA-B*51可能是易感基因,HLA-B*40、HLA-B* 48可能是保护性等位基因.     

维生素D受体基因ApaⅠ和TaqⅠ位点多态性与帕金森病的相关性研究

目的 探讨维生素D受体(vitamin D receptor,VDR)基因ApaⅠ和Taq Ⅰ位点多态性与帕金森病(Parkinson's disease,PD)遗传易感性的相关性.方法 采用聚合酶链反应-限制性片段长度多态性技术和基因测序方法,检测285例中国北方汉族散发PD患者与285名正常对照VDR基因ApaⅠ和TaqⅠ位点多态性,并比较两组基因型和等位基因频率的差异.结果 ApaⅠ和Taq Ⅰ位点基因型和等位基因频率在PD组和对照组之间差异均无统计学意义(P＞0.05).将样本按性别及发病年龄分组后比较,ApaⅠ位点各亚组间基因型频率和等位基因频率差异亦无统计学意义(P＞0.05),而TaqⅠ位点的基因型分布在男性PD组(168例)与男性对照组(1 60名)之间差异有统计学意义(x2=4.187,P=0.032,OR=2.149,95％CI:1.011～4.567),男性PD组T等位基因频率较男性对照组显著增高(x2=3.867,P=0.036,OR=2.064,95％CI:0.989～4.307).结论 VDR基因ApaⅠ位点多态性与PD风险间无相关性,但TaqⅠ可能是男性PD的风险因素.     

GP78基因多态性与冠心病相关

目的探讨GP78基因多态性与冠心病的相关性。方法 Taq Man SNP基因分型法对1109例(557例冠心病患者+552例对照者)无血缘关系的研究对象进行基因分型,并应用病例对照的研究方法进行相关性分析。结果GP78基因rs2617849位点的基因分型和等位基因频率在冠心病组和对照组之间的分布存在明显差异(P0.05),冠心病组携带TT基因型(TT vs CC+CT)和T等位基因高于对照组(P0.05),在排除吸烟、高血压、糖尿病和低密度脂蛋白胆固醇等混杂因素后,仍存在显著性差异(95%CI:1.035~1.736,P0.05)。结论 GP78基因的rs2617849位点多态性与冠心病相关,rs2617849的TT基因型和T等位基因可作为冠心病易感基因标记。     

新疆汉族HLA-DRB1基因多态性与再生障碍性贫血的相关性

目的探讨人类白细胞抗原(HLA)DRB1与再生障碍性贫血(AA)的相关性。方法采用序列特异性引物聚合酶链反应(PCR-SSP)DNA分型技术对43例新疆汉族AA患者(AA病例组)和200例新疆汉族人群作为健康对照者(健康对照组)进行HLA-DRB1基因分型,研究HLA-DRB1基因多态性与新疆汉族AA患者的相关性。结果 AA病例组和健康对照组的等位基因频率有相同之处,均表现为DRB1*15表达最高,同时DRB1*4、DRB1*7、DRB1*9、DRB1*12表达均较高,频率最低的均为DRB1*17;AA病例组中DRB1*8等位基因频率(13.73%)显著高于对照组(6.99%),差异有统计学意义(OR=2.202,P0.05);AA病例组DRB1*12、DRB1*14等位基因频率低于对照组,差异无统计学意义。其中AA病例组女性等位基因DRB1*12(5.41%vs 10.00%,OR=0.2079,P0.05)和AA病例组男性DRB1*14等位基因频率(2.11%)显著低于对照组(7.53%),差异有统计学意义(OR=0.1403,P0.05);AA病例组女性DRB1*15等位基因频率(27.45%)显著高于对照组(14.56%),差异有统计学意义(OR=2.433,P0.05)。结论 DRB1*08可能是AA患者的易感基因;DRB1*12可能是女性AA患者拮抗基因;DRB1*14可能是男性AA患者的拮抗基因;DRB1*15可能是女性AA患者的易感基因。     

The androgen receptor CAG and GGN repeat polymorphisms and prostate cancer susceptibility in African-American men: results from the Flint Men’s Health Study

Repeat lengths of the CAG and GGN microsatellites in exon 1 of the androgen receptor (AR) gene have been hypothesized to be associated with prostate cancer risk. In vitro studies have showed an inverse association between AR CAG and GGN repeat length and activity levels of the AR product. It is known that men of African descent have a higher incidence of and greater mortality from prostate cancer than men of Caucasian or Asian descent and, on average, a smaller number of repeats at AR CAG and GGN. Consistent with these findings, studies have also found increased AR protein expression levels in benign prostatic hyperplasia and prostatic diseased tissues from men of African descent. Despite these findings, limited studies have been conducted to evaluate the association between repeat lengths at AR CAG and prostate cancer risk in African Americans. Our study is the first such study to examine whether repeat length of the AR GGN repeat is associated with prostate cancer risk in African Americans. We found no evidence for an association between AR CAG or GGN repeat lengths and prostate cancer risk in a population-based sample of African Americans.     

Modifying effect of the AR gene trinucleotide repeats and SNPs in the AHR and AHRR genes on the association between persistent organohalogen pollutant exposure and human sperm Y:X ratio

Persistent organohalogen pollutants (POPs) have been suggested to be involved in changing the proportion of ejaculated Y-bearing sperm. The androgen receptor (AR), aryl hydrocarbon receptor (AHR) and aryl hydrocarbon receptor repressor (AHRR) may modulate the effect of POPs with regard to previously observed sperm Y:X ratio changes. The objective of this study was to investigate whether sperm Y:X ratio changes in subjects exposed to 2,2'4,4'5,5'-hexachlorobiphenyl (CB-153) and dichlorodiphenyl dichloroethene (p,p'-DDE) were modified by polymorphisms in the AR, AHR and AHRR genes. Semen for analysis of Y- and X-bearing sperm by two-colour fluorescence in situ hybridization and blood for leukocyte DNA genotyping and analysis of CB-153 and p,p'-DDE concentrations were obtained from 195 Swedish fishermen. The polymorphic CAG and GGN repeats in the AR and the R554K and P185A single-nucleotide polymorphisms in the AHR and AHRR genes, respectively, were determined by direct sequencing and allele-specific PCR. The effect of p,p'-DDE was modified by CAG or GGN repeat category in relation to the proportion of Y-bearing sperm (P = 0.005 and 0.02 for CAG and GGN, respectively). Moreover, p,p'-DDE, but not CB-153, levels were associated with Y-sperm proportion in men with CAG < 22 (P < 0.001), but not in those carrying CAG > or = 22 (P = 0.73). This association was even more pronounced in subjects carrying a short CAG repeat in combination with an AHRR G-allele. The association in regard to p,p'-DDE was found for GGN = 23 but not for the GGN < 23 or GGN > 23 subgroups (P = 0.01, 0.44 and 0.99, respectively). In conclusion The endocrine-disrupting action of POPs, in relation to the observed changes in sperm Y:X ratio, may be modulated by the genes involved in sex steroid and dioxin-mediated pathways.     

GGN repeat length and GGN/CAG haplotype variations in the androgen receptor gene and prostate cancer risk in south Indian men

The ethnic variation in the GGN and CAG microsatellites of the androgen receptor (AR) gene suggests their role in the substantial racial difference in prostate cancer risk. Hence, we performed a case-control study to assess whether GGN repeats independently or in combination with CAG repeats were associated with prostate cancer risk in South Indian men. The repeat lengths of the AR gene determined by Gene scan analysis, revealed that men with GGN repeats ≤21 had no significant risk compared to those with >21 repeats (OR 0.91 at 95% CI-0.52–1.58). However, when CAG repeats of our earlier study was combined with the GGN repeat data, the cases exhibited significantly higher frequency of the haplotypes CAG ≤19/GGN ≤21 (OR-5.2 at 95% CI-2.17–12.48, P < 0.001) and CAG ≤19/GGN > 21(OR-6.9 at 95%CI-2.85–17.01, P < 0.001) compared to the controls. No significant association was observed between GGN repeats and prostate-specific antigen levels and the age at diagnosis. Although a trend of short GGN repeats length in high-grade was observed, it was not significant (P = 0.09). Overall, our data reveals that specific GGN/CAG haplotypes (CAG ≤19/GGN ≤21 and CAG ≤19/GGN > 21) of AR gene increase the risk of prostate cancer and thus could serve as susceptibility marker for prostate cancer in South Indian men.     

Anthropometric measurements of Australian Aboriginal adults living in remote areas: Comparison with nationally representative findings

To compare body size measurements in Australian Aboriginals living in three remote communities in the Northern Territory of Australia with those of the general Australian population. Height, weight, waist and hip circumferences and derivative values of body mass index (BMI), waist‐hip ratio (WHR), waist‐height ratio (WHT), and waist‐weight ratios (WWT) of adult Aboriginal volunteers (n = 814), aged 25 to 74 years were compared with participants in the nationally representative ‘AusDiab’ survey (n = 10,434). The Aboriginal body habitus profiles differed considerably from the Australian profile. When compared to Australian females, Aboriginal females were taller and had lower hip circumference but had higher WC, WHR, WHT, and WWT (P < 0.01 for all). When compared with their Australian counterparts, Aboriginal males were shorter, had lower body weight, WC, hip circumference, BMI, and WHT but had higher WHR and WWT (P < 0.001 for all). Significantly more Aboriginal females were classified as overweight and or obese using cutoffs defined by WC and by WHR than by BMI. Aboriginal males were less often overweight and/or obese by BMI than their counterparts, but were significantly more often overweight or obese by WHR. There were significant variations in body size profiles between Aboriginal communities. However, the theme of excess waist measurements relative to their weight was uniform. Aboriginal people had preferential central fat deposition in relation to their overall weight. BMI significantly underestimated overweight and obesity as assessed by waist measurements among Aboriginals. This relationship of preferential central fat deposition to the current epidemic of chronic diseases needs to be explored further. Am. J. Hum. Biol., 2008. © 2008 Wiley‐Liss, Inc.     

Longitudinal anthropometric patterns among HIV-infected and HIV-uninfected women

INTRODUCTION: Previous studies suggest that indicators of central adiposity such as waist-to-hip ratio (WHR) and waist circumference may be altered by HIV infection, antiretroviral treatment, or both. METHODS: Waist and hip circumference and body mass index (BMI) were measured among participants of the Women's Interagency HIV Study semiannually from 1999 to 2004. Generalized linear models evaluated longitudinal patterns of these measures and associations with demographic and clinical characteristics. RESULTS: WHR was significantly larger, whereas BMI and waist and hip circumference were significantly smaller at almost all 11 semiannual visits among 942 HIV-infected women compared with 266 HIV-uninfected women. Among HIV-uninfected women, mean waist and hip circumference and BMI increased over the 5-year study period (waist: +4.1 cm or 4.4%, hip: +3.76 cm or 3.5%, and BMI +2.43 kg/m2 or 8.2%), whereas WHR remained stable. Among the HIV-infected women, waist and hip circumference, BMI, and WHR did not significantly change. Independent predictors of smaller BMI among HIV-infected women included white race, hepatitis C virus seropositivity, current smoking, higher viral load, and lower CD4 cell count. Independent predictors of larger WHR among HIV-infected women included age, white and other non-African American race, higher CD4 cell count, and protease inhibitor (PI) use. Use of a highly active antiretroviral therapy (HAART) regimen was not an independent predictor of BMI or WHR. CONCLUSIONS: HIV-infected women had higher WHRs compared with HIV-uninfected women, despite lower BMIs and waist and hip measurements. BMI and waist and hip circumference increased over 5 years among the HIV-uninfected women but remained stable in the HIV-infected women. Among HIV-infected women, PI use was associated with a larger WHR, although HAART use itself was not appreciably associated with BMI or WHR.     

成年人腰臀比和静态肺容量的关系

目的: 研究成年人腰臀比(WHR)和静态肺容量的关系。方法: 2008年7月至10月通过问卷和体检抽取黑龙江省部分地区19-81岁健康成年受试者1 307人,其中男性372人,女性935人,测量其身高、体重、腰臀比、肺功能和身体成分,以男性WHR≥0.86、女性WHR ≥0.82为中心性肥胖进行分组,分析WHR和静态肺容量关系。结果: 无论性别、腰臀比有随年龄、体重指数(BMI)增长而增大的趋势(P<0.01),中心性肥胖组的脂肪含量和体脂百分比都高于腰臀比正常组(P<0.01)。无论性别,WHR皆与补呼气量(ERV)独立负相关(P<0.05),中心性肥胖组ERV显著低于WHR正常组(P<0.05):男性下降11%,女性下降8%(P<0.05)。男性WHR与深吸气量(IC)独立正相关(P<0.05),中心性肥胖组IC较WHR正常组上升约6%(P<0.05)。女性WHR与每分通气量(MV)正相关(P<0.05),中心性肥胖组VT,MV较WHR正常组分别上升7%、6%(P<0.05)。结论: 腰臀比与ERV独立负相关。腰臀比升高是肺功能损伤的危险因素。腰臀比升高男性IC上升,女性MV上升可能与代偿ERV下降导致的动脉血氧分压有关。     

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.     

The relationship of body fat distribution to non-insulin-dependent diabetes mellitus in a Navajo community

The relationship between non-insulin-dependent diabetes mellitus (NIDDM) and body fat distribution (BFD) as measured by waist/hip circumference (WHR) was investigated in a Navajo community. A sample of 136 females and 89 males, 20 years and older, was recruited using a cluster-sampling design. Fifty percent of the females and 30.3% of the males are overweight [body mass index (BMI) equivalent of >120% ideal body weight]. Prevalence of NIDDM is 14% in females and 10.1% in males. The sample is characterized by central BFD (mean WHR=0.897±0.075, females and mean WHR=0.963±0.071, males). WHR is significantly related to age and BMI in males (P < 0.05), but not in females. Adjusted odds ratios for risk of NIDDM prevalence with increasing WHR category were estimated from a multiple logistic regression model which controlled for age and BMI. The odds ratio and 95% confidence interval (95% CI) is 2.19 (1.14, 4.19) for risk of NIDDM prevalence for a female in the middle BFD category compared to a female in the low BFD category. Risk increases to 3.63 (95% CI=1.25, 10.52) for a female in the highest BFD category. Although there is an increased risk of NIDDM prevalence with central BFD for males, it is not statistically significant. Preferential energy storage in abdominal fat depots may be a phenotypic expression of the “Thrifty Genotype,” which places American Indians at greater risk for metabolic disorders.