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1.
A complete linkage disequilibrium in a haplotype of three SNPs in Fat Mass and Obesity associated (FTO) gene was strongly associated with anthropometric indices after controlling for calorie intake and physical activity.
Kalantari, N, Keshavarz Mohammadi, N, Izadi, P, Gholamalizadeh, M, Doaei, S, Eini-Zinab, H, Salonurmi, T, Rafieifar, S, Janipoor, R, Azizi Tabesh, G
BMC medical genetics. 2018;(1):146
Abstract
BACKGROUND The underlying mechanism of the effect of FTO genotype on body mass index (BMI) and body composition is unknown. The objective of the study was to investigate the association of FTO gene polymorphisms with anthropometric indices in adolescent boys after adjustments for dietary intake and physical activity. METHODS In this school-based study, we enrolled 123 male adolescents without extra weight and 110 male adolescents with body mass index (BMI) higher than + 1 Z-score. The DNA samples were genotyped for the FTO gene polymorphisms by DNA Sequencing. BMI and body composition were assessed using bioelectrical impedance analyzer scale. Association of the FTO polymorphisms with Weight, height, BMI, body fat percent and skeletal muscle percent were investigated. Data on potential confounders (calorie intake and physical activity) were collected through the use of pre-tested questionnaires. RESULTS Adolescents with higher BMI and body fat percent and lower skeletal muscle percent were more likely to have a newly found haplotype of rs9930506, rs9930501 & rs9932754 (GGT) in the first intron of the FTO with complete linkage disequilibrium (LD) compared with those with the lower BMI (6.15;2.28-16.63), body fat percent (9.54;0.92-47.44) and higher skeletal muscle percent (9.26;1.85-46.38). This association was not changed after controlling for age. Additional adjustments for calorie intake and physical activity did not alter the association. CONCLUSIONS A haplotype in the first intron of the FTO gene had a strong association with obesity indices in adolescent boys after adjustments for calorie intake and physical activity. It's suggested that the FTO genotype exert its effects on adolescents' anthropometric indices as haplotype and through mechanisms other than changes in calorie intake and expenditure. TRIAL REGISTRATION This paper reports the first phase of a comprehensive interventional study (Interactions of Genetics, lifestyle and anthropometrics study or IGLA study) and is retrospectively registered in the Iranian Registry of Clinical Trials as IRCT2016020925699N2. Date registered: April 24, 2016. ( http://www.irct.ir/searchresult.php?id=25699&number=2 ).
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2.
Homocystine levels, polymorphisms and the risk of ischemic stroke in young Asian Indians.
Biswas, A, Ranjan, R, Meena, A, Akhter, MS, Yadav, BK, Munisamy, M, Subbiah, V, Behari, M, Saxena, R
Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association. 2009;(2):103-10
Abstract
BACKGROUND Homocysteine has been for a fairly long time been debated to be a risk factor for stroke. Opinions are divided as to whether raised levels of homocysteine seen in stroke patients are the cause or consequence of stroke. A large number of studies have been conducted in the Caucasian as well as on the Oriental population, which tend to suggest contradictory findings at many times. However, there have been no reports forthcoming from the Asian Indian population, which is a genetically different population than the previously studied populations. SUBJECTS AND METHODS In our present study, we looked at homocysteine levels and four commonly seen polymorphisms of homocysteine metabolizing enzymes and their respective prevalence in 120 acute onset ischemic stroke patients compared with an equal number of age and gender matched healthy population. We also tested the influence of folic acid dosage (5 mg OD) on the levels of homocysteine and the allied vitamin supplements, vitamin B12 and folate in smaller groups selected from the larger group. RESULTS AND CONCLUSIONS We found homocysteine levels to be significantly raised in the stroke population compared with healthy controls [patients: 12 micromol/L (range: 5.3-39.1 micromol/L), controls: 11.2 micromol/L (range: 6.2-14.2 micromol/L); P =0.001]. There was an almost total response to folic acid dosage as all hyperhomocysteinemic patients showed lowering of homocysteine levels in response to the dosage. The MTHFR 677 C > T polymorphisms showed association with both homocysteine levels as well as stroke (P < 0.001). Nutritional deficiency plays a dominant role in hyperhomocysteinemic conditions in our stroke population, however. Genetic determinants of homocysteine level may also have some part in determining hyperhomocysteinemic conditions in the Asian Indian populations.
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3.
apoE4 allele and the natural history of cardiovascular risk factors.
Scuteri, A, Najjar, SS, Muller, D, Andres, R, Morrell, CH, Zonderman, AB, Lakatta, EG
American journal of physiology. Endocrinology and metabolism. 2005;(2):E322-7
Abstract
The aims of the present study were to compare the longitudinal changes in traditional cardiovascular (CV) risk factors (blood pressure, BMI, total and HDL-cholesterol, triglycerides, and blood glucose) in men with and without the apolipoprotein (apo)E4 allele. Three hundred six men from the Baltimore Longitudinal Study of Aging, ranging in age from 20 to 92 yr, were studied. Repeated measurements of CV risk factors were performed over a median follow-up time of 7 yr (maximum 14.3 yr) for men. Longitudinal changes in these CV risk factors were analyzed by linear mixed-effects models. The prevalence of the apoE4 allele was 25.5%. apoE4 was independently associated with accelerated changes over time in fasting plasma glucose (+9.5% vs. no change in those without apoE4 in the 6th age-decade over 10 yr). No significant effect of apoE4 on longitudinal changes in total or HDL-cholesterol, triglycerides, or blood pressures was observed. In conclusion, apoE4 influences fasting plasma glucose and its changes over time. This could explain, in part, the increased CV risk associated with the apoE4 genotype observed in men.
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4.
SNPs and haplotypes in the S100B gene reveal association with schizophrenia.
Liu, J, Shi, Y, Tang, J, Guo, T, Li, X, Yang, Y, Chen, Q, Zhao, X, He, G, Feng, G, et al
Biochemical and biophysical research communications. 2005;(1):335-41
Abstract
The S100B gene locates in 21q22.3 and produces neurotrophin mainly in astrocytes of CNS which can act as an extensive marker of glial cell integrity. The synaptic destabilization hypothesis (GGF/SD) suggests that the functional deficiency of growth factors like S100B is involved in the etiology of schizophrenia and the S100B serum concentration is reported to be significantly increased in patients with acute schizophrenia and decreased in chronic schizophrenia patients. To validate the association between S100B and schizophrenia, 384 cases and 401 controls, all Chinese Han subjects, were recruited. Four SNPs V1 (-960C>G), V2 (-111C>T), V3 (2757C>G, rs1051169), and V4 (5748C>T, rs9722) were studied. And haplotype V3-V4 (G-C) showed a significant association with schizophrenia. Our study showed an association between schizophrenia and a possible susceptible haplotype V3-V4 (G-C) which possesses a genetic tendency for increased S100B expression. Our results suggest that S100B could be a susceptible gene for schizophrenia and provide indirect evidence for the GGF/SD hypothesis.
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5.
Association of the carboxyl-terminal PDZ ligand of neuronal nitric oxide synthase gene with schizophrenia in the Chinese Han population.
Zheng, Y, Li, H, Qin, W, Chen, W, Duan, Y, Xiao, Y, Li, C, Zhang, J, Li, X, Feng, G, et al
Biochemical and biophysical research communications. 2005;(4):809-15
Abstract
Several independent linkage studies have demonstrated that the 1q22 region is likely to harbor candidate schizophrenia susceptibility genes. Recently, some genetic variants within CAPON have been reported as exhibiting significant linkage disequilibrium to schizophrenia in Canadian familial-schizophrenia pedigrees. We examined nine single nucleotide polymorphisms (SNPs), which span an approximately 236-kb region of CAPON, in 664 schizophrenia cases and 941 controls in the Chinese Han population. We detected a significant difference in allele distributions of SNP rs348624 (P = 0.000017). Moreover, the overall frequency of haplotypes constructed from three SNPs including rs348624 showed significant difference between cases and controls (P = 0.000025). Our findings indicate that CAPON gene may be a candidate susceptibility gene for schizophrenia in Chinese Han population, and also provide further support for the potential importance of NMDAR-mediated glutamatergic transmission in the etiology of schizophrenia.
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6.
[Genetic variation of the cholesterol ester transfer protein gene and the prevalence of coronary artery disease. The AtheroGene case control study].
Blankenberg, S, Tiret, L, Bickel, C, Schlitt, A, Jungmair, W, Genth-Zotz, S, Lubos, E, Espinola-Klein, C, Rupprecht, HJ
Zeitschrift fur Kardiologie. 2004;:IV16-23
Abstract
BACKGROUND Various functional polymorphisms of the cholesteryl ester transfer protein ( CETP) gene influence CETP activity and the concentration of high-density lipoprotein (HDL) cholesterol. Beside other functional variants mainly the promoter polymorphism CETP/C-629A is currently discussed as a risk factor of coronary artery disease (CAD). We evaluated in a large case-control study the impact of various CETP genotypes and haplotypes on HDL concentration and the prevalence of CAD. METHODS AND RESULTS In 1214 patients with documented CAD as well as 754 population controls we determined the CETP/C-629A, TaqIB, I405V, R451Q, and A373P polymorphisms. All genotypes have an impact on the HDL concentration; univariate genotype and haplotype analyses demonstrate a significant effect of A-allel carriers on the elevation of HDL concentration. In addition, among all genotypes determined, the C-629A polymorphism is associated with the prevalence of CAD in a codominant fashion. Homozygous A-allel carriers reveal a relative risk of 0.6 (95% CI 0.44-0.82; P = 0.005) compared to the wild type. Adjustment for classical risk factors did not alter this association significantly, whereas after controlling for HDL concentration no independent significance between CETP/C-629A genotype and prevalence of CAD was observed anymore. CONCLUSION CETP genotypes have an significant but moderate impact on systemic HDL-cholesterol concentration. The A-allel of the CETP/C-629A polymorphism is associated with a reduced CAD risk. This risk reduction is probably mediated by elevated HDL-concentration. Whether genotyping of the CETP/C-629A polymorphism provides information over and above that obtained by HDL-cholesterol measurement has to be further investigated in various prospective studies.
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7.
Urinary catecholamine levels in daily life are elevated in women at familial risk of breast cancer.
James, GD, Berge-Landry Hv, Hv, Valdimarsdottir, HB, Montgomery, GH, Bovbjerg, DH
Psychoneuroendocrinology. 2004;(7):831-8
Abstract
Recent experimental research has shown that women facing the chronic stress of being at familial risk of breast cancer have greater neuroendocrine reactivity responses to stressful laboratory tasks. Whether this enhanced stress response also occurs outside the laboratory under daily life conditions is unknown. In the present study, urinary epinephrine and norepinephrine excretion rates at work (e.g. 11:00 AM-3:00 PM), home (e.g. 6:00 PM-10:00 PM) and during sleep (e.g. 10:00 PM-6:00 AM) were compared between 73 employed women with family histories of breast cancer in first degree relatives (FH+; age=36.8+/-8.7) and 81 without such family histories (FH-; age=38.1+/-9.4). Differences in sympathetic adrenal medullary responses to an ordinary life stressor (work) were assessed in naturalistic settings. Repeated measures MANCOVA with family history group as a fixed factor, body mass index as a covariate and daily microenvironment (work, home and sleep) as a repeating factor were conducted to evaluate whether catecholamine excretion rates differed between FH+ and FH- groups. The results revealed that women with family histories of breast cancer had a higher rate of epinephrine excretion while at work (p<0.005). In addition, women in the FH+ group were also more reactive to the stress of work, showing a greater percentage of increase in both epinephrine and norepinephrine from sleep to work (p<0.05). The results also indicated that the chronic stress effects associated with a family history of breast cancer were moderated by BMI, such that their impact was more pronounced and apparent when women were not obese. These findings support the idea that the heightened neuroendocrine reactivity to experimental stressors in women at familial risk of breast cancer also occurs when women encounter stressors in ordinary life (work stress). Additional research to explore the health consequences of increased reactivity in women at familial risk of breast cancer, and perhaps in individuals at familial risk of other life-threatening disease, would appear warranted.
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8.
How really rare are rare diseases?: the intriguing case of independent compound mutations in the long QT syndrome.
Schwartz, PJ, Priori, SG, Napolitano, C
Journal of cardiovascular electrophysiology. 2003;(10):1120-1
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9.
Serum homocysteine, folate and thermolabile variant of MTHFR in healthy Sri Lankans living in London.
Alagratnam, D, Wierzbicki, AS, Swaminathan, R, Turner, C, Wickramasinghe, SN
Atherosclerosis. 2000;(1):221-2
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10.
Developmental instability predicts individual variation in verbal memory skill after caffeine ingestion.
Jung, RE, Yeo, RA, Gangestad, SW
Neuropsychiatry, neuropsychology, and behavioral neurology. 2000;(3):195-8
Abstract
OBJECTIVE To determine the mediating effects of developmental instability on individual differences in response to caffeine. BACKGROUND Individual variation of drug effects might reflect broad genomic factors as well as the direct effects of specific alleles. The current study tested the hypothesis that individual differences in developmental instability, in part determined by genomic characteristics, would predict individual variation in the magnitude of caffeine-induced verbal memory deficits. Minor physical anomalies and fluctuating asymmetry were used as measures of developmental instability. METHOD One hundred participants were (1) administered one version of the Rey Auditory Verbal Learning Test; (2) given a dose of caffeine determined by body weight (3 mg/kg); (3) assessed for minor physical anomalies and fluctuating asymmetry; and (4) given an alternate randomized version of the Rey Auditory Verbal Learning Test. RESULTS Consistent with predictions, a composite measure of developmental instability predicted the magnitude of caffeine-induced memory decrements. CONCLUSIONS These results may have important implications for the genetic underpinnings of individual differences in drug effects.