Association of TRB3 Q84R polymorphism with polycystic ovary syndrome in Chinese women.
Reprod Biol Endocrinol. 2011 Apr 14;9(1):46
Authors: Zhang X, Fu L, Zhang Q, Yan L, Ma Y, Tu B, Liu N, Qiao J
ABSTRACT: BACKGROUND: Tribbles 3 (TRB3) affects insulin signalling by inhibiting insulin-stimulated Akt phosphorylation and subsequent activation. A single nucleotide polymorphism located in the second extron of the human TRB3 gene is thought to be associated with insulin resistance. The latter is a core abnormality in PCOS independent of obesity. The present study was designed to clarify the relationships of TRB3 Q84R polymorphism with PCOS in a Chinese women group. METHODS: A case-control study with two groups: PCOS group (n=336) and control group of infertility women for tubal and/or male factor (n=116) was performed. Genotyping of the TRB3 R84 variant was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: The frequency of genotype QQ in PCOS women was significantly lower, while genotype QR and RR were significantly higher than that in control group (p0.05). However, the difference disappeared after adjustment for BMI. At glucose1h, glucose2h and insulin2h point, the difference between QQ individuals and R84 allele carriers in PCOS women reached statistical significance during OGTT (p0.05). CONCLUSIONS: TRB3 Q84R polymorphism is associated with obesity and especially glucose metabolism and not associated with polycystic ovary syndrome because of compositional characteristics of phenotype in Chinese PCOS women.
PMID: 21492415 [PubMed - as supplied by publisher]
The allelic distribution of a single nucleotide polymorphism in the PDCD5 gene locus of Japanese non-small cell lung cancer patients.
Mol Med Report. 2008 Sep-Oct;1(5):667-71
Authors: Nanba K, Toyooka S, Soh J, Tsukuda K, Yamamoto H, Sakai A, Ouchida M, Kobayashi N, Matsuo K, Koide N, Kusaka K, Shimizu K, Date H
It has been reported that the rs1862214 single nucleotide polymorphism (SNP) in the programmed cell death 5 gene (PDCD5) is associated with smoking-related lung cancer risk and prognosis in a European population with a history of smoking. The aim of this study was to investigate the status and impact of SNPs in the PDCD5 locus of a Japanese population. We developed an assay based on real-time PCR with melting curve analysis for determining the rs1862214 SNP, and examined this SNP in 165 lung cancer patients and 180 healthy volunteers. Of the 165 lung cancer patients (107 smokers), 25 (17), 72 (47) and 68 (43) had the CC, CG and GG genotypes of rs1862214, respectively. Of the 180 volunteers (117 smokers), 31 (24), 81 (52) and 68 (41) had the CC, CG and GG genotypes of rs1862214, respectively. No significant difference in allelic distribution was found between Japanese patients and healthy controls, even among smokers. Based on the published data, the distribution of this SNP appears to be significantly different in Japanese and European populations. No significant difference in prognosis according to the SNP was observed, either in patients with a history of smoking or in the total number of patients. This too differs from the results from a European population. In conclusion, we developed a convenient real-time PCR-based assay for the genotyping of rs1862214 in the PDCD5 locus. The distribution of the rs1862214 SNP in our Japanese population differs from its distribution in a European population, and is not related to the risk of cancer or to poor prognosis in lung cancer. This suggests the presence of an ethnicity-related difference in the role of PDCD5 in the pathogenesis of lung cancer.
PMID: 21479467 [PubMed - in process]
Combined effect of pro- and anti-inflammatory cytokine gene polymorphisms on susceptibility to liver cirrhosis in Tunisian HCV-infected patients.
Hepatol Int. 2011 Feb 8;
Authors: Bouzgarrou N, Hassen E, Bahri O, Gabbouj S, Mami NB, Triki H, Chouchane L
PURPOSE: Chronic hepatitis C progression is commonly attributed to the continuous activation of the immune response with an increased production of pro-inflammatory cytokines, leading to fibrosis and ultimately to cirrhosis. On the contrary, anti-inflammatory cytokines, mainly interleukin (IL)-10 have a modulatory effect on hepatic fibrogenesis. The association between individual polymorphisms within cytokine genes and hepatitis C outcome is often weak and non-informative. Interestingly, it has been demonstrated that a combination of specific genotypes may be a more significant and powerful approach for predicting disease risk. AIM: This study is aimed at investigating the combined effect of single nucleotide polymorphism (SNP) in IL-18 (-607C/A, -137G/C), interferon (IFN)-γ (+874T/A) and IL-10 (-1082G/A) genes on cirrhosis risk in HCV-infected patients. METHODS: Seventy-seven chronic hepatitis C Tunisian subjects were included in this study. The patients were divided into two groups: the first included 31 non-cirrhotic patients, and the second included 46 liver cirrhosis patients. IL-18 genotyping was performed using the PCR amplification and the restriction fragment length polymorphism analysis (RFLP). IFN-γ and IL-10 polymorphisms were analyzed using the allele-specific PCR (AS-PCR). RESULTS: The combined high-risk genotype (IL-18 -607C/*, IL-18 -137G/*, IFN-γ +874T/*, IL-10 -1082A/A) frequency was compared between patients with and those without cirrhosis. Individuals were classified according the number of high-risk genotypes as follows: (0-2), patients with at most two high-risk genotypes; (3-4), patients with at least three of the high-risk genotypes. The logistic regression analysis showed that patients harboring 3-4 putative high-risk genotypes have a fivefold higher risk for developing cirrhosis in comparison to those harboring at most two high-risk genotypes (OR = 5.19; 95% CI = 1.49-18.05; p = 0.009). CONCLUSION: Our study showed that the co-inheritance of IL-18, IFN-γ and IL-10 specific high-risk genotypes is associated with a greater risk for liver cirrhosis.
PMID: 21484147 [PubMed - as supplied by publisher]
IGF gene polymorphisms and breast cancer in African-American and Hispanic women.
Int J Oncol. 2011 Mar 30;
Authors: Sarkissyan M, Mishra DK, Wu Y, Shang X, Sarkissyan S, Vadgama JV
Previous studies from our group and others have shown that increased circulatory levels of the ligand insulin-like growth factor 1 (IGF-1) and decreased levels of the predominant IGF-1 binding protein 3 (IGFBP-3) are associated with an increased incidence of breast cancer and poor outcome. Some studies suggest that, in addition to the influence of environmental factors on the levels of IGF-1 and IGFBP-3, alterations in their gene polymorphisms may play a significant role in the risk of cancer. In this study, we investigated the association between gene polymorphisms along the IGF axis and breast cancer, including the IGF-1 (CA) dinucleotide repeat, IGFBP-3 A-202C single nucleotide polymorphism, and the 2-bp deletion and (AGG)n repeat polymorphisms in the IGF type 1 receptor (IGF-IR). A total of 654 subjects, including both African-American and Hispanic/Latino subjects, were screened for various gene polymorphisms. IGF gene polymorphism genotyping was performed by PCR-GeneScan and PCR-RFLP methods. Our results demonstrated a significant association between the non-19/non-19 IGF-1 (CA)n polymorphism and breast cancer (OR=1.75; 95% CI=1.07-2.88; P=0.027). Furthermore, absence of the wild-type-19 allele and alleles <(CA)19 were strongly associated with breast cancer (OR=1.82; 95% CI=1.20-2.77; P=0.005 and OR=1.70; 95% CI=1.19-2.43; P=0.003, respectively). The association of the non-19/non-19 polymorphism with breast cancer was also more significant in premenopausal women (P=0.04). We did not find any significant association of the IGFBP-3 polymorphism with breast cancer. In the case of IGF-1R polymorphisms, the only significant trend was in the (AGG)5 allele; however, the frequency of this allele was very rare. In summary, our study demonstrated a significant association of IGF-1 polymorphisms and breast cancer. Future studies are necessary to understand the mechanistic value of these polymorphisms in breast cancer risk.
PMID: 21455574 [PubMed - as supplied by publisher]