Association of the Gln27Glu polymorphism of the beta-2-adrenergic receptor with preterm labor.

OBJECTIVES: To investigate a potential association between the beta-2-adrenergic receptor (B2AR) polymorphisms occurring at amino acid positions 16 (Arg16Gly) and 27 (Gln27Glu) and preterm labor. METHODS: Eighty patients with preterm labor and 76 control subjects were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: A significant association was found between Gln27Glu substitution and preterm labor (P=0.001). The frequency of Gly16 and Glu27 alleles were found to be higher in patients than in control women (0.54 vs. 0.48 and 0.42 vs. 0.26, respectively), and the odds ratio for the occurrence of preterm labor was 2.14 (95% CI, 1.32-3.46; P=0.002) for the Glu 27 allele. An early delivery was noted in 52.5% of patients. CONCLUSION: The Gln27Glu polymorphism of the B2AR gene may have a role in molecular pathogenesis of preterm labor. Glu27 allele in patients with preterm labor might be a risk factor for deliveries before 37 weeks of gestation.     

p53基因多态性与卵巢上皮性癌发病风险的关系

目的　探讨中国北方汉族妇女卵巢上皮性癌 (卵巢癌 )易感性与 p5 3基因第 4外显子的第 72密码子和第 3内含子多态性的关系。方法　应用序列特异性引物 ,以PCR技术检测 12 4例卵巢癌患者 (卵巢癌组 )和 12 8例健康妇女 (对照组 )的p5 3基因第 4外显子的第 72密码子和第 3内含子的基因型。结果　卵巢癌组和对照组脯氨酸 (Pro)、精氨酸 (Arg)等位基因频率分别为 5 3 2 %、4 6 8%和 4 6 1%、5 3 9%,两组比较 ,差异无显著性 (χ2 =2 5 6 3,P =0 10 9) ;卵巢癌组Pro/Pro、Pro /Arg、Arg/Arg 3种基因型频率分别为 2 9 0 %、4 8 4 %、2 2 6 %,与对照组 (2 1 1%、5 0 0 %、2 8 9%)相比 ,差异也无显著性 (χ2 =2 5 98,P =0 2 73) ;按病理类型分类 ,浆液性癌和宫内膜样癌两者间或分别与对照组间 ,其基因型频率与等位基因频率比较 ,差异均无显著性 (P >0 0 5 ) ;按手术病理分期分类 ,Ⅲ～Ⅳ期卵巢癌患者Arg等位基因及Arg/Arg基因型频率明显高于Ⅰ～Ⅱ期卵巢癌患者 (χ2 =7 4 94 ,P =0 0 0 6和 χ2 =8 318,P =0 0 0 4 )。卵巢癌组及对照组p5 3基因第 3内含子 16bp插入或缺序列 (PIN3)的A、A′等位基因频率分别为 94 8%、5 2 %及 94 5 %、5 5 %,两组比较 ,差异无显著性(χ2 =0 0 13,P =0 910 ) ;两组     

汉族妇女中p21 codon31单核苷酸多态性与宫颈癌易感性关系的研究

目的:研究汉族妇女中p21codon31单核苷酸多态性与宫颈癌易感性之间的关系。方法:用DNA抽提试剂盒从研究对象的外周血标本中抽提基因组DNA,其中宫颈癌患者226例(鳞状细胞癌215例,宫颈腺癌11例),正常对照组196例;用错配扩增突变检测PCR的方法测定p21codon31单核苷酸多态基因型。结果:宫颈鳞状细胞癌患者的p21codon31AGA(精氨酸)等位基因频率显著高于对照组(37.0%vs 24.0%,P<0.05,OR=1.9,95%CI=1.0~3.4);宫颈鳞状细胞癌与对照组之间的AGA/AGA、AGA/AGC和AGC/AGC等位基因型的分布差异有统计学意义,其中AGA/AGA(OR=2.5,95%CI=1.4~4.5)和AGA/AGC(OR=1.8,95%CI=1.6~2.8)等位基因型在宫颈鳞状细胞癌中的频率显著高于对照组。宫颈腺癌与对照组之间p21codon31单核苷酸多态性分布没有显著差异。结论:p21codon31AGA(精氨酸)等位基因可能是汉族妇女患宫颈鳞状细胞癌的一个危险因素。     

血清瘦素及瘦素受体基因Gln223Arg多态性与妊娠期糖尿病的相关性研究

目的:探讨血清瘦素水平及瘦素受体基因Gln223Arg多态性与妊娠期糖尿病的相关性。方法:应用放射免疫分析法(RIA)及聚合酶链反应-限制性内切酶片段长度多态性(PCR-RFLP)技术,检测62例妊娠期糖尿病(GDM)患者及60例正常孕妇(NGT)血清瘦素及瘦素受体基因Gln223Arg多态性。结果:(1)GDM组血清瘦素水平为14.2±4.3μg/L,NGT组为10.1±2.6μg/L,二者差异有统计学意义(P<0.05)。(2)GDM组孕妇瘦素受体基因Gln223Arg基因型GG、(GA+AA)频率分别为61.29%、38.71%,正常孕妇组分别为81.67%、18.33%,两组比较差异有统计学意义(P<0.05);GDM组孕妇瘦素受体基因Gln223Arg等位基因频率G、A分别为77.42%、22.58%,正常孕妇组孕妇分别为89.17%、10.83%,两组比较差异有统计学意义(P<0.05);(3)GDM组中基因型为GA+AA的孕妇瘦素水平为15.3±4.1μg/L,GG基因型为13.5±3.7μg/L,二者差异有统计学意义(P<0.05)。结论:瘦素,瘦素受体基因Gln223Arg多态性与GDM相关,GDM患者瘦素受体基因Gln223Arg变异可能影响血清瘦素水平。     

Polymorphisms in the endothelial nitric oxide synthase gene may be protective against preeclampsia in a Chinese population

The association between the endothelial nitric oxide synthase (eNOS) gene with vascular diseases in Western populations and with severe preeclampsia (PE) in the Japanese population have been demonstrated, lacing the data in Chinese population. The authors examine the association between PE and 2 polymorphisms of the eNOS gene in a Chinese population, consisting of 92 pregnant women with PE and 256 healthy controls. All were genotyped for the Glu298Asp polymorphism in exon 7 and the number of 27 base pair repeats in intron 4 of the eNOS gene. The frequencies of both the variant T allele and eNOS 4a (small allele with 4 repeats of 27 bp) were significantly lower in the PE group than in the control group. The genotype distribution of Glu298Glu, Glu298Asp, and Asp298Asp in eNOS exon 7 and bb type and ab type in eNOS intron 4 revealed statistically significant differences between control and PE groups. This is the first study to evaluate the association between 2 polymorphisms in the maternal eNOS gene with PE simultaneously in a Chinese population. Similar to the findings in Western populations, polymorphisms in the eNOS gene may be protective against PE in a Chinese population, in contrast to the results in the Japanese population.     

Prevalence of the insulin receptor substrate-1(IRS-1) Gly972Arg and the insulin receptor substrate-2(IRS-2) Gly1057Asp polymorphisms in PCOS patients and non-diabetic healthy women

Objective  

The aim of our study was to investigate the frequency and compare the prevalence of IRS-1Gly972Arg and IRS-2 Gly1057Asp polymorphisms in PCOS patients and non-diabetic healthy women.     

Alterations of the FSH and LH receptor genes and evaluation of sperm ultrastructure in men with idiopathic hypergonadotropic hypogonadism

Purpose

Gonadotropins, interacting with their gonadal receptors, play a key role in sexual development, reproductive functions and metabolism. In this study we performed the genetic analysis of FSHR and LHR and semen investigation in 14 infertile men with normal level of T and elevated levels of FSH and/or LH in the absence of other causes of infertility.

Methods

Sperm parameters were analysed following WHO (2010) guidelines and sperm morphology by Transmission Electron Microscopy (TEM) analysis mathematically elaborated. FSHR and LHR gene mutations have been searched by PCR technique, followed by DHPLC analysis and direct sequencing.

Results

In FSHR, we found no difference in the frequency between Ala or Thr at position 307, Ser was at codon 680 in all subjects. Three patients had an heterozygous mutation at codon 419. Three intronic polymorphisms (rs2091787, rs6708637, rs1922464) were significantly found compared to controls; the single allele frequency and the odds ratio were calculated. Two new variants: the Cys338Arg and the Gln123Glu were detected in two different patients. Regarding LHR, three patients were heterozygous for the known variant Glu354Lys and two for Ile374Thr. Intronic polymorphisms were not identified. A new variant, the Val144Ile was found. By the routine semen analysis, variable seminal conditions in this group of patients was observed, on the contrary TEM data mathematically elaborated showed a homogeneous decrease in fertility index and increase in sperm pathologies such as apoptosis and immaturity.

Conclusions

The obtained results suggest that a deeper examination of spermatozoa, achieved by the use of more powerful tools such as TEM or molecular analysis, are advisable in patients with hypergonadotropic hypogonadism.     

Glutathione-S-transferase and p53 polymorphisms in cervical carcinogenesis

OBJECTIVE: To investigate the clinical significance of glutathione-S-transferase GSTM1, GSTT1 and p53 codon 72 polymorphisms in cervical carcinogenesis. METHODS: GSTM1, GSTT1 and p53 codon 72 polymorphisms together with human papillomavirus (HPV) types were examined in a total of 198 cervical smear samples using multiplex polymerase chain reaction (PCR) and PCR restriction fragment length polymorphism (RFLP) techniques. RESULTS: Forty-two patients with high-grade squamous intraepithelial lesion (HSIL) had higher frequency of high-risk HPV and null GSTT1 genotype than 102 with low-grade SIL (LSIL) and 54 controls. Thirty-one patients with HSIL had also statistically higher frequency of null GSTT1 genotype than 28 with LSIL among 69 patients with high-risk HPV. There was no statistical difference in p53 Arg, Arg/Pro and Pro genotypes between SILs and controls with or without high-risk HPV. CONCLUSION: GSTT1 null genotype in cervical cell samples may be associated with more severe precancerous lesions of the cervix in a Japanese population. The p53 codon 72 polymorphism is unlikely to be related to HPV status and the onset of cervical cancer.     

Associations between two single nucleotide polymorphisms in the adiponectin gene and polycystic ovary syndrome.

In the present study we determined whether genetic variability in the gene encoding adiponectin is associated with polycystic ovary syndrome (PCOS). Altogether 143 Caucasian women with PCOS and 245 healthy controls were genotyped for two single nucleotide polymorphisms (SNPs) in exon 2 and intron 2 in the adiponectin gene. Single-point analysis was expanded to pair-of-loci haplotype analysis to examine the estimated haplotype frequencies of the two SNPs, of unknown phase, in the PCOS and control groups. Estimated haplotype frequencies were assessed using the maximum-likelihood method, employing an expectation-maximization algorithm. A significantly different allele distribution in intron 2 SNP was observed between the groups, with the T allele being significantly reduced in the PCOS group (25.9%) compared with the control group (32.7%) ( p = 0.047), at an odds ratio of 0.72 (95% confidence interval 0.52-0.99). Otherwise, the allele and genotype distributions in either SNP were not statistically different between the groups. In haplotype estimation analysis, there was a lower frequency of the haplotype T-T in the PCOS group (25.9%) than in the control group (32.7%) ( p = 0.058). We conclude that polymorphisms of the adiponectin gene may be implicated in individual susceptibility to PCOS.     

Polycystic ovary syndrome and the single nucleotide polymorphisms of methylenetetrahydrofolate reductase: a pilot observational study

Polycystic ovary syndrome (PCOS), insulin resistance and overall mortality due to diabetes and coronary artery disease are higher in South Asians than in Caucasians. Aims: We compared the prevalence of the C677T and A1298C single nucleotide polymorphisms in the methylenetetrahydrofolate reductase gene in South Asian and Caucasian women, its association with folate and homocysteine (Hcy) metabolism, and its relevance to future atherogenic events. Methods and results: 71 women were recruited for the study: South Asian PCOS (21) plus controls (9) and Caucasian PCOS (25) plus controls (16). Anthropometric and laboratory parameters were compared. South Asian PCOS women were significantly hyperandrogenic and exhibited a greater degree of insulin resistance. Caucasian PCOS women had higher plasma Hcy concentrations with a 1.9 times higher frequency of the T allele than the South Asian PCOS group. In the presence of this variant allele, plasma Hcy levels appear to be higher in both PCOS groups. The South Asians had a 1.8 times higher frequency of the C allele than the Caucasians; however, the overall frequency was comparable in the two PCOS groups. The frequency of homozygosity, i.e. TT677 and CC1298, was 7.2% and 4.9% in the Caucasians and 0% and 16.6% in the South Asian recruits, respectively. Dietary inadequacies in the South Asian women can influence their plasma folate and B12 concentrations resulting in hyperhomocysteinemia which, in combination with dyslipidaemia and insulin resistance, can lead to long-term atherogenic consequences. CONCLUSIONS: Current data suggests that the mechanisms of atherothrombosis have separate pathways in the two ethnic groups. Larger studies exploring the current theme need to be carried out in the PCOS groups to obtain adequate insight.     

Polymorphism at codon 72 of the p53 gene is not associated with endometriosis in a Japanese population

OBJECTIVE: Endometriosis is inherited as a complex trait, which means that multiple susceptibility genes interact with each other and the environment to produce the phenotype. Previous studies have implicated p53, a tumor suppressor gene, as a factor in the development of the disease. In a Japanese population, we investigated the frequency of the p53 polymorphism in women affected with endometriosis. METHODS: We compared the distribution of the p53 codon 72 polymorphism in endometriosis cases (n = 111) and population controls consisting of female neonates (n = 180) by using polymerase chain reaction restriction fragment-length polymorphism analysis in a Japanese population. RESULTS: The frequencies of the three p53 genotypes, Arginine (Arg)/Arg, Arg/Proline (Pro), and Pro/Pro in controls were 39.4%, 41.7%, and 18.9 %, respectively. The crude genotype frequencies in the endometriosis cases were similar to those of the controls (35.2%, 48.6%, and 16.2%, respectively). Using the Arg/Arg genotype as the reference, the odds ratios of the Arg/Pro and Pro/Pro genotypes were 1.30 (95% confidence interval [CI] 0.72-1.86, P =.33) and 0.96 (95% CI 0.47-1.94, P =.91), respectively. Thus, there were no significant differences in the frequency of the p53 codon 72 polymorphism between endometriosis cases and controls in this population. The endometriosis cases with severe disease only were also evaluated, but no significant difference was observed in the frequency of the polymorphism between this subgroup and the controls. CONCLUSION: Our findings suggest that the p53 codon 72 polymorphism is unlikely to be associated with endometriosis in Japanese women.     

Leptin receptor gene polymorphisms in severely pre-eclamptic women.

Variants of the leptin receptor gene (LEPR) may modulate the effect of elevated serum leptin levels in pre-eclampsia. The aim of our study was to evaluate the LEPR gene polymorphisms Lys109Arg (A109G) and Gln223Arg (A223G) in severely pre-eclamptic women. In a case-control study, we analyzed blood samples from 124 severely pre-eclamptic patients and 107 healthy control women by the polymerase chain reaction-restriction fragment length polymorphism method. The Pearson chi2 test was used to estimate odds ratios (OR) and 95% confidence intervals (CI). The association was adjusted for maternal age, pre-pregnancy body mass index and primiparity with logistic regression analysis. Pregnant women with the LEPR 223G allele (223A/G or 223G/G genotype) had almost double the risk of developing severe pre-eclampsia compared with patients with the 223A/A genotype (adjusted OR = 1.92, 95% CI: 1.07-3.41). Genotype variants of LEPR A109G alone did not affect the risk of severe pre-eclampsia. Haplotype estimation of A109G and A223G polymorphisms of the LEPR gene revealed that the G-A haplotype versus other pooled haplotypes was significantly less common in the pre-eclamptic group (p < 0.01), while the G-G haplotype versus others was overrepresented among severely pre-eclamptic patients (p < 0.01), compared with controls. In conclusion, our data indicate that LEPR A223G polymorphism may individually modify the risk of severe pre-eclampsia.     

Beta2-adrenergic receptor gene polymorphisms and pregnancy outcome

AIMS: The association between alleles at two loci of the polymorphic beta2-adrenergic receptor (beta2AR) gene and pregnancy outcome was determined. METHODS: In a case-control study, buccal swabs obtained from 159 mother-infant pairs after a preterm or term birth were analyzed by gene amplification and endonuclease digestion for polymorphisms at codons 16 and 27 of the beta2AR gene. RESULTS: Homozygosity for allele A at codon 16 (Arg-16) occurred in 26 (20.5%) of 127 mothers with a term birth and in none of the mothers who had a spontaneous preterm birth (p=0.002). Conversely, 24 of 32 (75.0%) mothers with a spontaneous preterm birth, as compared to 58 of 127 (45.7%) mothers with term births, were Arg-16/ allele G (Gly-16) heterozygotes (p=0.003). There was no relation between pregnancy outcome and infant genotype at codon 16 or maternal or infant genotypes at codon 27. The alleles at codon 16 and 27 were in linkage disequilibrium and the combinations of Arg-16-Gln-27 homozygosity (p=0.04) and Arg-16/Gly-16-Gln homozygous (p=0.01) were associated with a decreased and increased rate of spontaneous preterm birth, respectively. CONCLUSION: At codon 16 of the beta2-AR gene, maternal Arg-16 homozygosity protects against, and Gly-16 predisposes to spontaneous preterm birth.     

Germline polymorphism of p53 codon 72 in gynecological cancer

OBJECTIVE: To investigate the biological significance of single nucleotide polymorphism at codon 72 of the p53 gene in the development of gynecological cancer. METHODS: p53 codon 72 polymorphism was examined in a total of 354 blood samples from 95 normal, 83 cervical, 108 endometrial and 68 ovarian cancer cases using polymerase chain reaction and restriction fragment length polymorphism techniques. RESULTS: When p53 codon 72 genotype was classified into two subgroups of Arg/Arg and Arg/Pro + Pro/Pro, the Arg/Arg genotype was associated with an increased risk for the development of endometrial cancer (OR = 1.86, 95% CI = 1.06 to 3.26) compared with the Arg/Pro + Pro/Pro genotype (P = 0.0301). The Arg allele also increased the risk of endometrial cancer (OR = 1.42, 95% CI = 0.93 to 1.52) compared with the Pro allele, but no statistical difference was found (P = 0.1031). There was no significant difference in the genotype or allele prevalence between control subjects and cervical or ovarian cancer patients. CONCLUSION: Homozygous Arg at codon 72 of the p53 gene may be a risk factor for developing endometrial cancer in a Japanese population.     

WAF1 genotype and endometrial cancer susceptibility

The WAF1 protein, which is a downstream mediator of p53, functions as a universal inhibitor of cyclin-dependent kinases. The functional link between p53 and WAF1 suggests the possibility that alteration in WAF1 function constitutes an alternative mechanism to p53 inactivation. However, there are few reports describing somatic mutations of the WAF1 gene in various human malignancies. A polymorphism in the WAF1 gene, a C-to-A transversion at codon 31 resulting in the change of a serine (Ser) to an arginine (Arg), is well known. We found this substitution in 42 of 54 endometrial carcinoma patients. Allele frequency was 0.44/0.56 for the codon 31 polymorphism (Ser/Arg), the difference of allele frequency between patients and normal controls being significant (0.59/0.41 in normal controls). In addition, individuals carrying the codon 31 Arg allele had a tendency to develop histologically high-grade (odds ratio, 6. 11) and clinically advanced tumors. We investigated the association of the Arg allele with the known risk factors of endometrial carcinomas. Statistical analyses of 42 cases and 32 controls carrying the codon 31 Arg allele identified hypertension (odds ratio, 4.33) and family history of cancer (odds ratio, 2.81) as positive risk factors. This implies that these two parameters may be associated with a tendency to develop endometrial carcinomas in individuals carrying the codon 31 Arg allele of the WAF1 gene.     

Polycystic ovary syndrome and the single nucleotide polymorphisms of methylenetetrahydrofolate reductase: a pilot observational study

Polycystic ovary syndrome (PCOS), insulin resistance and overall mortality due to diabetes and coronary artery disease are higher in South Asians than in Caucasians. Aims: We compared the prevalence of the C677T and A1298C single nucleotide polymorphisms in the methylenetetrahydrofolate reductase gene in South Asian and Caucasian women, its association with folate and homocysteine (Hcy) metabolism, and its relevance to future atherogenic events. Methods and results: 71 women were recruited for the study: South Asian PCOS (21) plus controls (9) and Caucasian PCOS (25) plus controls (16). Anthropometric and laboratory parameters were compared. South Asian PCOS women were significantly hyperandrogenic and exhibited a greater degree of insulin resistance. Caucasian PCOS women had higher plasma Hcy concentrations with a 1.9 times higher frequency of the T allele than the South Asian PCOS group. In the presence of this variant allele, plasma Hcy levels appear to be higher in both PCOS groups. The South Asians had a 1.8 times higher frequency of the C allele than the Caucasians; however, the overall frequency was comparable in the two PCOS groups. The frequency of homozygosity, i.e. TT677 and CC1298, was 7.2% and 4.9% in the Caucasians and 0% and 16.6% in the South Asian recruits, respectively.

Dietary inadequacies in the South Asian women can influence their plasma folate and B12 concentrations resulting in hyperhomocysteinemia which, in combination with dyslipidaemia and insulin resistance, can lead to long-term atherogenic consequences. Conclusions: Current data suggests that the mechanisms of atherothrombosis have separate pathways in the two ethnic groups. Larger studies exploring the current theme need to be carried out in the PCOS groups to obtain adequate insight.     

Association between polymorphisms in DNA repair genes (XRCC1 and XRCC7) and risk of preeclampsia

Purpose

Although the exact genes involved in preeclampsia (PE) are still not fully discovered, an important role for oxidative stress in its pathogenesis is accepted. XRCC1 (MIM: 194360) and XRCC7 (MIM: 600899) play a crucial role in the DNA repair pathways. Functional polymorphisms in XRCC1 (Arg194Trp and Arg399Gln) and XRCC7 (G6721T) may be risk factors for PE. In the present study, the association between the genetic polymorphisms of XRCC1 and XRCC7 and risk of PE is investigated.

Methods

The present case–control study was performed on 151 preeclapmtic patients, and a total of 344 normal pregnant women, as a control group. Control women had no history of pregnancies with PE.

Results

Neither polymorphism of Arg194Trp XRCC1 nor polymorphism of G6721T XRCC7 associated with the risk of PE. The Gln/Gln genotype of Arg399Gln XRCC1 polymorphism increased the risk of PE (OR?=?2.39, 95?% CI: 1.38–4.14, P?=?0.002). Statistical analysis revealed that the haplotype “194Arg-399Gln” showed higher frequency among PE patients compared to the controls (OR?=?1.65, 95?% CI: 1.23–2.19, P?=?0.001).

Conclusions

The present results suggest that the 399Gln allele of the XRCC1 is significant risk factor for PE development.     

血管紧张素转化酶基因插入/缺失多态性及胰岛素受体亚单位-1基因Gly972Arg突变对出生体重的影响

目的 探讨血管紧张素转化酶(angiotensin converting enzyme,ACE)基因插入/缺失(insertion/deletion,I/D)多态性及胰岛素受体亚单位-1(insulin receptor substrate-1,IRS-1)基因Gly972Arg突变对出生体重的影响.方法 将入选296例新生儿分为两组,适于胎龄儿组222例,小于胎龄儿组74例,于生后3 d哺乳前检测血糖、胰岛素,计算HOMA-IR值比较两组的胰岛素敏感性;应用PCR-RFLP方法分析IRS-1基因Gly972Arg突变及ACE基因I/D多态性,比较各基因型组间出生体重、出生体重百分位.结果 小于胎龄儿组HOMA-IR值(Ln对数转换后)为0.217±0.367,高于适于胎龄儿组0.001±0.378(P<0.01).IRS-1基因突变组与野生型相比,出生体重较轻,分别为(2270.00±638.97)g及(2655.53±774.78)g,出生体重百分位较低,分别为(13.12±10.76)%及(39.87±30.18)%,差异均有统计学意义(P<0.05).ACE基因DD基因型出生体重百分位为(27.05±24.70)%,低于ID基因型(39.21±29.37)%及Ⅱ基因型(44.69±27.91)%,差异有统计学意义(P<0.05).同时具有ACE基因DD基因型及IRS-1基因突变者出生体重最低(2516.00±230.28)g,低于正常组(2919.87±717.04)g及具有一种基因多态性组(2572.44±724.20)g;其出生体重百分位也最低(18.00±14.89)%,低于正常组(44.97±27.07)%及具有一种基因多态性组(26.95±20.70)%,差异均有统计学意义(P<0.05).结论 IRS-1基因Gly972Arg突变及ACE基因I/D多态性可能对胎儿宫内发育和出生体重具有影响.     

HPV16/18 prevalence in cervical lesions/cancers and p53 genotypes in cervical cancer patients from India

OBJECTIVES: The HPV16/18 code for an oncoprotein-E6, which binds to p53 tumor suppressor protein and degrades the protein via ubiquitination. A common polymorphism of p53 in exon 4 codon 72, resulting in either proline (Pro) or arginine (Arg), affects HPV16/18 E6-mediated degradation of p53 protein in vivo. Hence, in the current study we investigated the prevalence of HPV16/18 in cervical lesions and the distribution of p53 genotypes in cervical cancers and normal healthy women. METHODS: DNA from 337 Indian women with invasive cervical cancers, 164 women with clinically normal cervix, 64 women with low-grade squamous intraepithelial lesions (LSIL), and 5 women with high-grade squamous intraepithelial lesions (HSIL) was examined for the presence of HPV16/18 using consensus primers in a polymerase chain reaction (PCR), and the specific HPV type was identified by Southern hybridization of the PCR product using HPV16/18 type-specific nucleotide sequences as probes. Further, 134 women with cervical cancers and 131 healthy women were used to determine the frequency of p53 genotypes, Pro/Pro, Arg/Arg, and Pro/Arg, using peripheral blood cell DNA to indicate the constitutional genotypes and allele-specific primers, in a PCR-based assay. RESULTS: We observed a prevalence of HPV16/18 in 77% (258/337) of cervical cancer patients, 38% (24/64) of LSILs, 4 of 5 HSILs, and 15.2% (25/164) of normal healthy women. The frequency of distribution of the three genotypes of p53 codon 72 in a subgroup of the HPV16/18-positive cervical cancer patients was Pro/Pro 0.18 and Arg/Arg 0.26, with the heterozygous Pro/Arg 0.56, differing significantly from the genotype frequency in the normal healthy women (chi(2) = 6.928, df = 2, P < 0.05). CONCLUSIONS: A high prevalence of HPV16/18 was observed in the cervical cancers. The prevalence in LSILs confirms HPV16/18 infection as an early event and further indicates a role in progression of lesions. The p53 genotype distribution indicated that women homozygous for Arg genotype were at a 2.4-fold higher risk for developing HPV16/18-associated cervical carcinomas, compared to those showing heterozygous Pro/Arg genotype (odds ratio 2.4, 95% confidence interval 1.89 to 3.04).     

Association of p53 codon 72 polymorphism with risk of hypopharyngeal squamous cell carcinoma in Taiwan.

BACKGROUND: p53 polymorphism at codon 72 is a known risk marker for various malignancies, but it has not been studied in hypopharyngeal cancer. This study investigated the genotype distribution of p53 codon 72 polymorphism in hypopharyngeal cancer patients and non-cancer controls matched for age, gender, alcohol consumption and smoking habit. METHODS: Genomic DNA was extracted from peripheral blood cells of 53 patients with hypopharyngeal cancer and 53 non-cancer controls. Codon 72 polymorphism of p53 was identified by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: Patients with hypopharyngeal cancer had higher frequencies of Pro/Pro (26.4% vs. 13.2%) and Pro/Arg (51.0% vs. 45.3%) but lower frequencies of Arg/Arg (22.6% vs. 45.1%) compared to controls. Compared to Arg/Arg genotypes, Pro/Pro genotypes had a relative risk of hypopharyngeal cancer of 3.667 (95% confidence interval, 1.16-11.56; p = 0.03). As a group, patients with Pro/Pro or Arg/Pro who were carriers of the Pro allele had a higher relative risk of hypopharyngeal cancer compared to Arg homozygous carriers (odds ratio, 2.415; 95% confidence interval, 1.04-5.64; p = 0.04). CONCLUSION: This study demonstrated that p53 codon 72 Pro homozygosity is associated with a higher risk of developing hypopharyngeal cancer.