Letter to the Editor: Genetic Contributions to Childhood Obesity: Association of Candidate Gene Polymorphisms and Overweight/Obesity in Korean Preschool Children

No abstract available.

Extremely low frequency electromagnetic field in combination with beta-Lapachone up-regulates the genes of non-homologous end joining

Background and purpose: Non-homologous end joining [NHEJ] is the major pathway for removing DNA double strand breaks lesions. NHEJ is considered to be a resistant factor against chemotherapy induced neuropathy. beta-Lapachone [beta-Lap] is one of the antineoplastic agents which is shown to have anti neuroinflammatory effects. Extremely low frequency [<300 Hz] electromagnetic field [EMF] is shown to decrease NHEJ genes expression. Morphine [Mor] is associated with reducing effect on DNA repair and induce DNA damages. The goal of this study was to evaluate the effect of combination treatment of beta-Lap, morphine [Mor] and EMF on expression of NHEJ related genes [XRCC4, Ku70, Ku80, DNA-PKcs and LIG4]

Materials and methods: SH-SY5Y cells [epithelial neuroblasts] were treated with four combinational treatments of beta-Lap [2.0 and 3.2 microM], Mor [5.0 microM] and EMF [50 Hz, 0.50 mT, "15 min field on/15 min field off"] and mRNA levels of XRCC4, Ku70, Ku80, DNA-PKcs and LIG4 were evaluated by quantitative real-time PCR and primers specific for the examined genes. The experiments were done in triplicates

Results: No significant alteration in the mRNA levels of NHEJ related genes was observed in "beta-Lap alone" and "beta-Lap + Mor" treated cells. The expression levels of NHEJ related genes were significantly increased in "beta-Lap + EMF" and "beta-Lap + Mor + EMF". Multiple linear regression analysis showed that the effect of EMF and Mor on NHEJ related genes expression is opposite to the effect of beta-Lap

Conclusion: In overall, combination of beta-Lap, Mor and EMF leads to increased expression of NHEJ related gene expression. This effect may lead to decreased sensitivity of SH-SY5Y cells against beta-Lap and can improve its neuroprotective property which might be hopeful for its clinical applications

Susceptibility to methamphetamine dependence associated with high transcriptional activity alleles of VNTR polymorphism in the promoter region of monoamine oxidase A [MAOA]

Background and purpose: Monoamine oxidase A [MAOA, Xp11.3; OMIM: 309850] can modulate the level of neurotransmitters in the central nervous system. A 30 bp variable number of tandem repeat [VNTR] genetic polymorphism on the promoter region of the MAOA can modulate the transcriptional activity of the gene. Association between this polymorphism and dependency to methamphetamine was investigated

Subjects and methods: A total of 65 methamphetamine abusers [52 males and 13 females] and 635 healthy controls [525 males and 110 females] were included in the present case-control study. Genotypic analysis for the MAOA VNTR polymorphism was determined by conventional PCR. Based on transcriptional activity of the VNTR alleles, the alleles were categorized into two classes: L allele [2R and 3R alleles] and H allele [3.5R, 4R and 5R alleles], which have low and high transcriptional activities, respectively

Results: Our data show that the H allele significantly increases the risk of methamphetamine dependence in males [OR = 2.03, 95% CI: 1.04-3.67, P = 0.037]. The H allele seems positively associated with the risk of dependency to methamphetamine among females, but the observed OR did not reach the significance level, probability due to small sample size of the patients

Conclusion: The present study supports the role of the VNTR polymorphism on the promoter region of the MAOA on methamphetamine dependence

Association between consanguinity and survival of marriages

The present study was performed to investigate the association between consanguineous marriages and divorce risk. A total of 496 couples at divorce time and 800 couples from general population who have no plan for divorce [as control group] were included in the study. Compared to unrelated marriages, first cousin [OR = 0.39, 95% CI: 0.27-0.56, P < 0.001], first cousin once removed [OR = 0.18, 95% CI: 0.05-62, P = 0.006] and second cousin marriages [OR = 0.37, 95% CI: 0.17-0.78, P = 0.009] decreased the risk of divorce. The Cox proportional hazards regression analysis revealed that the survival of marriage was lower significantly for unrelated marriages than first cousin marriages, after adjusted for educational level [HR = 0.48, 95% CI: 0.35-0.67, P < 0.001]. The present findings indicate that consanguinity has some protective role [s] against divorce and also survival of marriages increased among consanguineous marriages. Considering that divorce rate is affected by several factors, replication of present findings in other populations is recommended

Letter to the Editor: Presence of Evolutionary Pressures or Genotyping Error

No abstract available.

Association between Exudative Age-related Macular Degeneration and the G6721T Polymorphism of XRCC7 in Outdoor Subjects

PURPOSE: To investigate whether the G6721T polymorphism (rs.7003908) of the non-homologous end-joining DNA repair XRCC7 gene contributes to the development of exudative age-related macular degeneration (ARMD). METHODS: The present case-control study consisted of 111 patients with exudative ARMD and 112 sex frequency-matched healthy controls that were randomly selected from unrelated volunteers in the same clinic. Genotypes were determined by the Restriction Fragment Length Polymorphism (PCR-RFLP) based method. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for ARMD risk associated with polymorphism of XRCC7. In all analysis the GG genotype was considered to be the reference genotype. RESULTS: There was no significant association between genotypes of XRCC7 and susceptibility to ARMD. Considering the significant difference in age distribution between cases and controls, age was used as a covariate in further analysis. After ORs were adjusted for age, the same result was observed. In the next step we stratified our subjects into outdoor and indoor groups according to their job titles. The outdoor and indoor patients were occupationally exposed to sunlight and not exposed to sunlight, respectively. Our present study showed that among indoor subjects there was no association between XRCC7 polymorphism and susceptibility to ARMD. However, among outdoor subjects, the GT + TT genotypes compared to the GG genotype increased the risk of ARMD (OR, 3.13; 95% CI, 1.04-9.39; p = 0.042). CONCLUSIONS: Our study revealed that the T allele of the G6721T polymorphism of XRCC7 increased the risk of ARMD among outdoor subjects.

Apolipoprotein E (APOE) Polymorphisms and Susceptibility to Breast Cancer: A Meta-Analysis / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Apolipoprotein E (APOE, MIM: 107741) has three functionally distinct isoforms of the protein (E2, E3, and E4), encoded by corresponding alleles epsilon2, epsilon3, and epsilon4, which have been well described. Findings from previous studies investigating association between APOE polymorphisms and breast cancer risk have been inconsistent. The present meta-analysis was conducted in order to investigate association of APOE polymorphisms with risk of breast cancer. MATERIALS AND METHODS: Several electronic databases were used for identification of studies containing information on APOE polymorphisms and breast cancer risk published up to January 2012. We identified 10 eligible studies, including 3,835 subjects (2008 patients, and 1,827 healthy controls), that reported on polymorphisms of APOE and risk of breast cancer. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were obtained using a fixed and random-effects models. RESULTS: Among studies reported from Asia, an association of the epsilon4 allele with increased risk of breast cancer, in comparison with the epsilon3 allele, was observed (OR, 1.56; 95% CI, 1.19 to 2.04; p=0.001). It should be noted that allele epsilon2 showed no association with breast cancer risk. Among Caucasians, neither the epsilon4 (OR, 0.99; 95% CI, 0.83 to 1.17; p=0.917) nor the epsilon2 (OR, 0.92; 95% CI, 0.72 to 1.17; p=0.514) allele showed an association with susceptibility to breast cancer, when compared with the epsilon3 allele. Carriers of the epsilon4 allele (E4E4, E4E3, and E4E2 genotypes), in comparison with the E3E3 genotype, showed an association with elevated risk of breast cancer only among Asians (OR, 1.75; 95% CI, 1.23 to 2.47; p=0.002). No publication bias was detected. CONCLUSION: This meta-analysis suggest that the APOEepsilon4 allele is a low-penetrant risk factor for development of breast cancer.

Influence of genetic polymorphisms of glutathione S-transferases Tl and Ml on serum lipid parameters

To determine the effect of genetic polymorphisms of glutathione S-transferase theta 1 [GSTTl] and GSTM1 on serum levels of lipid parameters. We conducted this cross-sectional study on 152 adult healthy subjects [54 females and 98 males] from June 2004 to September 2004. The participants in our study were recruited from the Research Clinic in Abarku [Yazd province, central part of Iran]. There were unrelated Iranian Muslims. The genotypes of GSTTl and GSTM1 were determined using a polymerase chain reaction based method. After an overnight fasting, serum lipid indices including triglyceride [TG], total cholesterol [TC] and high density lipoprotein cholesterol [HDL-C] were measured. There were significant partial correlation coefficients between levels of TG [r= -0.4833, df=48, P<0.001] andTG/HDL-C ratio [r= -0.4041, df=48, P=0.004] and numbers of active GST genotypes in females after controlling for age and body mass index [BMI]. In males, the level of TG increased as a function of numbers of active GST genotypes after controlling for age and BMI [r= +0.2082, df=94, P=0.042]. There were significant differences between females and males. Data show that genetic polymorphisms of GSTM 1 and GSTTl modulate levels ofTG, andTG/HDL-C in females

Identification of human chromosome segments that have high homology with rat genomic DNA

This study was conducted to determine the location of DNA segment with homology to the rat conserved genomic DNA in human chromosomes. The labeled rat genomic DNA was hybridized with normal human [male] metaphases. The study of 74 metaphases after fluorescence in situ hybridization showed 371 twin-spot signals on human chromosomes. Statistical analysis indicated that the specific accumulation of signals on lq22-qter, 2p2, 3p21-p23, 4q3, 6q2, 8pl2-pter, llpl2-pter, llql2-qter, 12q2, 13p, 15p, 16q2, 21ql2-qter, Yql-qter, and Xq2 was not r and om. Results of stepwise multiple linear regressions indicated that number of mapped oncogenes [Beta = 1.092; t = 7.552; P<0.001] and density of mapped oncogenes on chromosomes [Beta = -0.832; t = -5.751; P<0.001] have significant effects on number of double-spots on human chromosomes. These data reflects the evolutionary conservation between rat DNA and human DNA at the above-mentioned b and s

Report of VNTR with 13 repeats linked to phenylalanine hydroxylase locus in unaffected members of two PKUfamilies

Phenylketonuria [PKU] is one of the most common metabolic inborn diseases caused by mutations in the phenylalanine hydroxylase [PAH] gene. This gene is linked to a variable number of tandem repeats [VNTR] region which is a polymorphic marker that facilitates the implementation of prenatal diagnosis and carrier screening. In this study, VNTR with 13 repeats that has not been reported previously was observed in 2 PKU families from Fars province, south of Iran. This allele showed 4% frequency in normal individuals

Changes in the pp1 and mRNA level and pp1 activity of ascites hepatomas at different cell growth rates

It is now well established that the type 1 alpha of serine / threonine protein phosphatases [PP1 alpha] may be implicated in malignant phenotype. Although the PP1 alpha mRNA level increased in livers at preneoplastic stages of hepatocarinogenesis and all of examined rat ascites hepatomas, unexpectedly, dramatically decreased in some of primary hepatomas. In order to elucidate the low level of PP1 alpha mRNA in some of primary hepatomas and investigate any correlation between cell growth rates and change [s] of both PP1 alpha mRNA and PP1 activity, the present experiments were done. The most important aspects of the present study are: 1] The PP1 alpha mRNA level may decreased in ascites hepatoma AH -109A cells harvested from a highly bloody ascites compared to ones harvested from a milky ascites. 2] The spontaneous PP1 activity in particulate fraction of AH-7974F showed a positive correlation with cell growth rate. 3] There was no correlation between proliferation rate of AH-7974F and the amount of PP1 alpha catalytic subunit as well as potential PP1 activity in particulate fraction. Therefore, it is suggested that the PP1 alpha mRNA level may decrease in the primary hepatomas with low proliferation rate which were under very bad nutritional conditions

Regional assignment of the rat alpha - fetoprotein gene [AFP] to chromosome 14 p 21 - p 22

The gene encoding alpha fetoprotein [locus symbol Afp] was assigned to rat chromosome p21-p22 using fluorescence in situ hybridization method. The present result suggests that there is a conserved syntenic group between human 4q11-q13, mouse 5F-G, and rat 14p21-p22