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PubMed2006

Polymorphisms in genes involved in GH1 release and their association with breast cancer risk.

The regulation of growth hormone 1 (GH1) and insulin-like-growth factor-1 (IGF-1) release is under the influence of three pituitary hormones [growth hormone releasing hormone (GHRH), ghrelin (GHRL) and somatostatin (SST)], which act in an autocrine/paracrine fashion in the breast. By binding to their respective receptors, they control cell proliferation, differentiation and apoptosis in a GH1/IGF-1-dependent manner. We investigated single nucleotide polymorphisms (SNPs) in the GHRH, GHRHR, GHRL, GHSR, SST and SSTR2 gene regions in a Polish and a German cohort of 798 breast cancer cases and 1011 controls. Our study revealed an association of a novel TC repeat polymorphism in the SST promoter with a decreased breast cancer risk in the Polish study population [odds ratio (OR), 0.65; 95% confidence interval (CI), 0.44-0.96]. The closely linked SNP IVS1 A+46G showed the same trend. For both polymorphisms the association was stronger in women above the age of 50 (OR, 0.33; 95% CI, 0.14-0.76 and OR, 0.39; 95% CI, 0.18-0.87, respectively). The protective effect of these polymorphisms was confirmed in a haplotype analysis among women above 50 years of age and carrying the two variant alleles (OR, 0.37; 95% CI, 0.17-0.80). In the independent German population, we observed slightly decreased ORs among women above the age of 50 years. In the SSTR2 gene, carriers of the promoter 21/21 TG repeat genotype were at a decreased breast cancer risk (OR, 0.62; 95% CI, 0.41-0.94) compared to carriers of the other genotypes in the Polish population. Furthermore, we identified a protective effect of the GHRHR C-261T SNP in both populations (joint analysis CT+TT versus CC: OR, 0.80; 95% CI, 0.65-0.99). This effect was carried by a haplotype containing the protective allele. Thus, our study concludes a possible protective influence of distinct polymorphisms in genes involved in GH1 release on breast cancer risk.

Adolescent↗
PubMed2005

Preprohypocretin polymorphisms in Parkinson disease patients reporting "sleep attacks".

STUDY OBJECTIVES: Previously, we found a significant association between the dopamine D2 receptor gene polymorphism Taq IA and sudden onset of sleep in patients with Parkinson disease. Here we evaluated the association between the preprohypocretin (-909T/C), (-22C/T), and (-20C/A) polymorphisms and sudden onset of sleep in the same population of patients with Parkinson disease. DESIGN: We conducted an association study analyzing the distribution of preprohypocretin polymorphisms in Germanic, caucasian Parkinson disease patients with and without sudden onset of sleep, matched according to drug therapy, disease duration, sex, and age. SETTING: Movement disorders section at a university hospital. PARTICIPANTS: 132 Parkinson disease patients with sudden onset of sleep and 132 Parkinson disease patients without sudden onset of sleep. INTERVENTIONS: Blood samples were taken from each participant and used for DNA extraction. Polymorphisms were analyzed by established polymerase chain reaction protocols or direct sequencing. MEASUREMENTS AND RESULTS: The variant allele T of the (-909T/C) preprohypocretin polymorphism was more commonly found in Parkinson disease patients with sudden onset of sleep. Statistical analysis showed that there were significant differences in the genotype (P = .024) and allele (P = .018) distribution between both groups. For heterozygous and homozygous carriers of allele T, the genotype relative-risk estimates for the presence of sudden onset of sleep were 2.01 (95% confidence interval: 0.76-5.34) and 2.81 (95% confidence interval: 1.09-7.25), respectively. CONCLUSIONS: Our results show a significant association between the (-909T/C) preprohypocretin polymorphism and sudden onset of sleep in Parkinson disease. However, we could not demonstrate any interaction between the Taq IA and (-909T/C) polymorphisms with respect to the occurrence of sudden onset of sleep, suggesting that multiple genetic factors may contribute to the pathogenesis of this phenomenon.

Alleles↗
PubMed2004

Human immunodeficiency virus type 1 superinfection was not detected following 215 years of injection drug user exposure.

Evidence for human immunodeficiency virus type 1 (HIV-1) superinfection was sought among 37 HIV-1-positive street-recruited active injection drug users (IDUs) from the San Francisco Bay area. HIV-1 sequences from pairs of samples collected 1 to 12 years apart, spanning a total of 215 years of exposure, were generated at p17 gag, the V3-V5 region of env, and/or the first exon of tat and phylogenetically analyzed. No evidence of HIV-1 superinfection was detected in which a highly divergent HIV-1 variant emerged at a frequency >20% of the serum viral quasispecies. Based on the reported risk behavior of the IDUs and the HIV-1 incidence in uninfected subjects in the same cohort, a total of 3.4 new infections would have been expected if existing infection conferred no protection from superinfection. Adjusted for risk behaviors, the estimated relative risk of superinfection compared with initial infection was therefore 0.0 (95% confidence interval, 0.00, 0.79; P = 0.02), indicating that existing infection conferred a statistically significant level of protection against superinfection with an HIV-1 strain of the same subtype, which was between 21 and 100%.

Adult↗
PubMed2005

Prion biology relevant to bovine spongiform encephalopathy.

Bovine spongiform encephalopathy (BSE) and chronic wasting disease (CWD) of deer and elk are a threat to agriculture and natural resources, as well as a human health concern. Both diseases are transmissible spongiform encephalopathies (TSE), or prion diseases, caused by autocatalytic conversion of endogenously encoded prion protein (PrP) to an abnormal, neurotoxic conformation designated PrPsc. Most mammalian species are susceptible to TSE, which, despite a range of species-linked names, is caused by a single highly conserved protein, with no apparent normal function. In the simplest sense, TSE transmission can occur because PrPsc is resistant to both endogenous and environmental proteinases, although many details remain unclear. Questions about the transmission of TSE are central to practical issues such as livestock testing, access to international livestock markets, and wildlife management strategies, as well as intangible issues such as consumer confidence in the safety of the meat supply. The majority of BSE cases seem to have been transmitted by feed containing meat and bone meal from infected animals. In the United Kingdom, there was a dramatic decrease in BSE cases after neural tissue and, later, all ruminant tissues were banned from ruminant feed. However, probably because of heightened awareness and widespread testing, there is growing evidence that new variants of BSE are arising "spontaneously," suggesting ongoing surveillance will continue to find infected animals. Interspecies transmission is inefficient and depends on exposure, sequence homology, TSE donor strain, genetic polymorphism of the host, and architecture of the visceral nerves if exposure is by an oral route. Considering the low probability of interspecies transmission, the low efficiency of oral transmission, and the low prion levels in nonnervous tissues, consumption of conventional animal products represents minimal risk. However, detection of rare events is challenging, and TSE literature is characterized by subsequently unsupported claims of species barriers or absolute tissue safety. This review presents an overview of TSE and summarizes recent research on pathogenesis and transmission.

Animals↗
PubMed1987

Small intestinal motor activity--its role in gut homeostasis and disease.

The study of small intestinal motor activity has certainly emerged from relative obscurity to a position where it may indeed become an important clinical tool. Modern technology has led to a considerable increase in our understanding of the physiology of motor function and has brought us to a stage where small intestinal motility is amenable to study in man. It is clear that coordinated motor function of the small intestine is central to integrated digestive function. Normal patterns, and in particular normal variants, are still being defined, and both the investigator and the clinician need to be particularly aware of interspecies, intersubject and interregional variations. While in some instances, abnormal motility is clearly related to an underlying disorder of intestinal neuromuscular function, in others, and in particular in functional gastrointestinal disorders, the overall experience of intestinal motility recordings in man is still too limited to allow us to declare with confidence whether reported abnormalities are, indeed, truly aberrant patterns or whether they are causally related to a given patient's symptoms.

Gastrointestinal Diseases↗
PubMed2005

Contribution of single nucleotide polymorphisms within FCRL3 and MAP3K7IP2 to the pathogenesis of Graves' disease.

CONTEXT: Recently six DNA variants, two of which (M55V and 001Msp) are present in nuclear factor-kappaB inhibitors SUMO-4 and MAP3K7IP2 and four of which (fcrl3_3, fcrl3_4, fcrl3_5, and fcrl3_6) modulate nuclear factor-kappaB binding and production of the B cell surface molecule FCRL3, have been reported to be associated with a number of autoimmune diseases. OBJECTIVE: The aim of this study was to investigate the association of these polymorphisms with disease in a large UK Caucasian Graves' disease (GD) data set. DESIGN: The study was a case-control association study of six polymorphisms. SETTING: The study was conducted at a UK academic department of medicine. PATIENTS OR PARTICIPANTS: Study population included 1056 GD patients and 864 controls. INTERVENTIONS: There were no interventions. MAIN OUTCOME MEASURES: Tests for association with disease were measured. RESULTS: No association with disease was found for the M55V single-nucleotide polymorphism (SNP). Association was, however, found between GD and the 001Msp SNP [odds ratio (OR) 1.19 (95% confidence interval [CI]) 1.03-1.37], fcrl3_3 SNP [OR 1.17 (95% CI 1.02-1.34)], fcrl3_5 SNP [OR 1.18 (95% CI 1.04-1.35)], and fcrl3_6 SNP [OR 1.20 (95% CI 1.05-1.36)]. The 001Msp SNP was found to be associated with the presence of TSH receptor autoantibodies [OR 1.75 (95% CI 1.09-2.79)]. CONCLUSION: Functional evidence suggests that the 001Msp, fcrl3_3, fcrl3_5, and fcrl3_6 SNPs could cause changes in B cell signaling and activation pathways that could account for their association with GD. Further replication in independent data sets and fine mapping of the surrounding gene regions are needed to confirm the magnitude of the effect and location of the etiological variant(s) present within these gene regions.

Adaptor Proteins, Signal Transducing↗
PubMed2006

TGFbeta1 polymorphisms and late clinical radiosensitivity in patients treated for gynecologic tumors.

PURPOSE: To investigate the association between six transforming growth factor beta1 gene (TGFbeta1) polymorphisms (-1.552delAGG, -800G>A, -509C>T, Leu10Pro, Arg25Pro, Thr263Ile) and the occurrence of late normal tissue reactions after gynecologic radiotherapy (RT). METHODS AND MATERIALS: Seventy-eight women with cervical or endometrial cancer and 140 control individuals were included in the study. According to the Common Terminology Criteria for Adverse Events version 3.0 (CTCAEv3.0) scale, 25 patients showed late adverse RT reactions (CTC2+), of whom 11 had severe complications (CTC3+). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), single base extension and genotyping assays were performed to examine the polymorphic sites in TGFbeta1. RESULTS: Homozygous variant -1.552delAGG, -509TT, and 10Pro genotypes were associated with the risk of developing late severe RT reactions. Triple (variant) homozygous patients had a 3.6 times increased risk to develop severe RT reactions (p=0.26). Neither the -800A allele, nor the 25Pro allele or the 263Ile allele were associated with clinical radiosensitivity. There was perfect linkage disequilibrium (LD) between the -1.552delAGG and the -509C>T polymorphisms, and tight LD between the -1.552/-509 and the Leu10Pro polymorphisms. Haplotype analysis revealed two major haplotypes but could not distinguish radiosensitive from nonradiosensitive patients. CONCLUSIONS: The present study shows that homozygous variant TGFbeta1 -1.552delAGG, -509TT, and 10Pro genotypes may be associated with severe clinical radiosensitivity after gynecologic RT.

Adult↗
PubMed2000

Common paraoxonase gene variants, mortality risk and fatal cardiovascular events in elderly subjects.

Recent studies indicate that the enzyme paraoxonase may be an important modulator of cardiovascular disease risk because of its ability to protect LDL from oxidation. We tested for association between two functional variants of the paraoxonase gene (Met-55/Leu and Gln-192/Arg) and both all-cause mortality and fatal cardiovascular disease. This was done within a population-based study among subjects aged 85 years and over in a cross-sectional and a prospective design. In the cross-sectional analysis, the distribution of both paraoxonase genotypes was found to be similar in the subset of 364 elderly subjects who were born in Leiden, The Netherlands, as compared with 250 young subjects whose families originated from the same geographical region. The polymorphisms were in strong linkage disequilibrium (P<0.00001) and the frequency of the haplotype carrying both risk alleles was not lower in the elderly than in the young (0.313 vs. 0.284). The complete cohort of 666 elderly subjects was followed over 10 years. The risk of all-cause and cardiovascular mortality was not increased in elderly subjects with the paraoxonase Leu/Leu (RR, 1.1 [95% CI, 0.9-1.5] and 1.3 [95% CI, 0.8-2.0], respectively) or the Arg/Arg genotype (RR, 0. 9 [95% CI, 0.7-1.2] and 0.7 [95% CI, 0.4-1.3], respectively). In a subset of patients with diabetes, the all-cause mortality risk was elevated in Arg/Arg carriers (RR, 2.1 [95% CI, 0.8-5.8]) but this did not reach statistical significance. Analysis of genotype combinations did not yield significant associations with mortality. The paraoxonase gene variants, previously associated with coronary artery disease, are thus not likely to have a major effect on the risk of fatal cardiovascular disease in the population at large. Adverse effects of the gene variants might be observed in subjects exposed to factors that enhance oxidative stress such as diabetes.

Adult↗
PubMed2006

Sequence variations in PCSK9, low LDL, and protection against coronary heart disease.

BACKGROUND: A low plasma level of low-density lipoprotein (LDL) cholesterol is associated with reduced risk of coronary heart disease (CHD), but the effect of lifelong reductions in plasma LDL cholesterol is not known. We examined the effect of DNA-sequence variations that reduce plasma levels of LDL cholesterol on the incidence of coronary events in a large population. METHODS: We compared the incidence of CHD (myocardial infarction, fatal CHD, or coronary revascularization) over a 15-year interval in the Atherosclerosis Risk in Communities study according to the presence or absence of sequence variants in the proprotein convertase subtilisin/kexin type 9 serine protease gene (PCSK9) that are associated with reduced plasma levels of LDL cholesterol. RESULTS: Of the 3363 black subjects examined, 2.6 percent had nonsense mutations in PCSK9; these mutations were associated with a 28 percent reduction in mean LDL cholesterol and an 88 percent reduction in the risk of CHD (P=0.008 for the reduction; hazard ratio, 0.11; 95 percent confidence interval, 0.02 to 0.81; P=0.03). Of the 9524 white subjects examined, 3.2 percent had a sequence variation in PCSK9 that was associated with a 15 percent reduction in LDL cholesterol and a 47 percent reduction in the risk of CHD (hazard ratio, 0.50; 95 percent confidence interval, 0.32 to 0.79; P=0.003). CONCLUSIONS: These data indicate that moderate lifelong reduction in the plasma level of LDL cholesterol is associated with a substantial reduction in the incidence of coronary events, even in populations with a high prevalence of non-lipid-related cardiovascular risk factors.

Black People↗
PubMed1997

T2-weighted hyperintense MRI lesions in the pons in patients with atherosclerosis. Amsterdam Vascular Medicine Group.

BACKGROUND AND PURPOSE: Pontine hyperintense lesions (PHL) on T2-weighted MRI have been recognized recently. Histopathological findings resemble periventricular leukoaraiosis, and a vascular etiology has been suggested. We studied the frequency and the associated factors of PHL in patients with symptomatic atherosclerosis. METHODS: Two independent observers assessed brain MRIs in a prospective cohort of patients with symptomatic atherosclerosis. Only patients in whom both observers scored PHL on T2- and proton density-weighted images, but not on T1-weighted images, were considered to have the lesion. RESULTS: We studied 229 patients 31% presenting with ischemic stroke, 31% with myocardial infarction, and 38% with peripheral artery disease. Both observers scored PHL in 23% of all patients. Patients with PHL were significantly older and had more lacunar infarcts and periventricular leukoaraiosis than patients without PHL. There were more women, more hypercholesterolemic and diabetic patients, and more cortical infarcts on MRI (P = NS). After logistic regression the presence of leukoaraiosis (odds ratio, 2.4; 95% confidence interval, 1.6 to 3.4) and lacunar infarcts (odds ratio, 2.2, 95% confidence interval, 1.5 to 3.1) remained independently associated with PHL. PHL was more common in patients with ischemic strokes (39%) than in patients with myocardial infarctions (11%) or peripheral artery disease (19%) (P < .001). CONCLUSIONS: We found that PHL on T2- and proton density-weighted MR images are often found in patients with symptomatic atherosclerosis. The association with periventricular leukoaraiosis and lacunar infarcts suggests that PHL is a variant of leukoaraiosis, with possibly the same pathophysiology. The clinical symptoms and consequences of PHL, however, are not yet clear.

Age Distribution↗
PubMed2004

Lipoprotein lipase gene polymorphisms and blood pressure levels in the Northern Chinese Han population.

The lipoprotein lipase (LPL) gene has been investigated extensively in linkage studies and in studies of its association with lipid profiles and coronary artery disease (CAD), and this gene has also been reported to have an association with hypertension. In our previous linkage study on 148 Chinese hypertensive families, the regions at or near the LPL gene were found to be associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP). Thus the LPL gene is a logical candidate gene for involvement in the underlying cause of essential hypertension (EH). In the present study, we identified 22 sequence variants by directly sequencing 10 exons and flanking regions of the LPL gene, and investigated the occurrence of 3 of these variants, IVS4-214C>T, 7754C>A and S447X, in a case-control study including 501 normotensive (NT) subjects and 497 EH subjects. In males, the frequencies of the genotypes of each of the 3 variants did not differ significantly between the NT and EH groups. Among the EH group in females, ANCOVA revealed no significant difference in blood pressure levels according to the 7754C>A genotype. However, in female, the distribution of the 7754C>A genotype and the frequency of the A allele of 7754C>A differed significantly between the NT and EH groups (p=0.032 and p=0.027, respectively) with 0.78 (95% confidence interval (CI): 0.56 to 1.07; p=0.12) of odds ratio for the A allele. Moreover, haplotype analysis revealed that T-A-C and T-C-G haplotypes (in the order of IVS4-214C>T, 7754C>A and S447X) were statistically more frequent in the NT group than in the EH group in females and males, respectively. Our indivisual single nucleotide polymorphism (SNP) analysis did not provide substantial evidence of an association between polymorphisms in the LPL gene and hypertension status and/or blood pressure levels in this cohort, but the more powerful haplotypes analysis suggested an association between the LPL gene and hypertension.

Adult↗
PubMed2002

Further studies of genetic susceptibility to Graves' disease in a Russian population.

BACKGROUND: Graves' disease (GD) is a polygenic autoimmune thyroid syndrome. Some of the genes implicated in its pathogenesis may encode thyroid-stimulating hormone receptor (TSHR) and estrogen receptors 1 (ESR1) and 2 (ESR2). We examined dinucleotide repeat polymorphisms in the ESR1 and ESR2 genes and D727E amino acid substitution in the TSHR gene for possible association with GD in a Russian population. MATERIAL/METHODS: The polymorphic regions of the target genes were amplified by polymerase chain reaction (PCR) on the basis of genomic DNA isolated from blood of 78 unrelated Russian patients with GD and 93 control subjects. To detect the D727E TSHR polymorphism, the PCR product was additionally digested with Eco72I restriction endonuclease. The genotype and allele frequencies in the groups studied were compared by c2 test. The odds ratios and 95% confidence intervals (CI) were calculated to assess the strength of the relationship between the polymorphisms tested and GD. RESULTS: For polymorphic dinucleotide microsatellites at ESR1 and ESR2, no significant difference was observed in allele frequencies between affected and nonaffected patients. For the D727E TSHR polymorphism, the E allele and the DE genotype were significantly more frequent (p<0.0001) in patients with GD than in control subjects. CONCLUSIONS: The D727E variant of the TSHR gene is associated with Graves' disease in a Russian population. The E727 allele and the heterozygous D727E genotype are related to higher risk of the disease. No association with GD was found for polymorphic microsatellites of the ESR1 and ESR2 gene.

Adult↗
PubMed2006

Migraine and MTHFR C677T genotype in a population-based sample.

OBJECTIVE: Migraine with aura is associated with increased risk of stroke. The MTHFR C677T genotype has been associated with increased risk of migraine in selected clinical samples and with elevated homocysteine, a risk factor for stroke. We assessed the association of the MTHFR C677T variant with migraine and the mediating effect of cardiovascular risk factors and metabolic markers of genotype status. METHODS: We compared adult migraineurs with aura (MA; n = 187), without aura (MO; n = 226), and nonmigraineurs (n = 1,212) from the population-based Genetic Epidemiology of Migraine study. RESULTS: Compared with the wild-type genotype, the T/T genotype was associated with increased odds of MA (odds ratio [OR], 2.05; 95% confidence interval, 1.2-3.4; p < 0.006), with a trend of increasing numbers of T alleles (OR, 1.40; 95% confidence interval, 1.1-1.8; p < 0.007). ORs were slightly attenuated after adjusting for homocysteine. INTERPRETATION: Risk of MA is associated with MTHFR C674T homozygosity, independent of other cardiovascular risk factors.

Adult↗
PubMed2006

Carrier frequency of mutation 657del5 in the NBS1 gene in a population of Polish pediatric patients with sporadic lymphoid malignancies.

Nijmegen breakage syndrome (NBS) is a human autosomal recessive disease characterized by genomic instability and enhanced cancer predisposition, in particular to lymphoma and leukemia. Recently, significantly higher frequencies of heterozygous carriers of the Slavic founder NBS1 mutation, 657del5, were found in Russian children with sporadic lymphoid malignancies, and in Polish adults with non-Hodgkin lymphoma (NHL). In addition, the substitution 643C>T (R215W) has also been found in excess among children with acute lymphoblastic leukemia (ALL). In an attempt to asses the contribution of both mutations to the development of sporadic lymphoid malignancies, we analyzed DNA samples from a large group of Polish pediatric patients. The NBS1 mutation 657del5 on one allele was found in 3 of 270 patients with ALL and 2 of 212 children and adolescents with NHL; no carrier was found among 63 patients with Hodgkin lymphoma (HL). No carriers of the variant R215W were detected in any studied group. The relative frequency of the 657del5 mutation was calculated from a total of 6,984 controls matched by place of patient residence, of whom 42 were found to be carriers (frequency = 0.006). In the analyzed population with malignancies, an increased odds ratio for the occurrence of mutation 657del5 was found in comparison with the control Polish population (OR range 1.48-1.85, 95% confidence interval 1.18-2.65). This finding indicates that the frequency of the mutation carriers was indeed increased in patients with ALL and NHL (p < 0.05). Nonetheless, NBS1 gene heterozygosity is not a major risk factor for lymphoid malignancies in childhood and adolescence.

Adolescent↗
PubMed2004

A polymorphism of the beta1-adrenergic receptor is associated with low extraversion.

BACKGROUND: We examined the possibility that allelic variation leading to alterations in beta(1)-adrenergic function might be present in persons with elevated social anxiety-related traits. METHODS: A sample of 504 undergraduate college students were phenotyped on a personality inventory (the NEO-Personality Inventory-Revised) and measures of shyness and social anxiety and genotyped for two beta(1) adrenergic (ADRB1 gene) polymorphisms: a serine/glycine substitution at amino acid 49 (Ser49Gly) and an arginine/glycine substitution at residue 389 (Arg389Gly). We hypothesized that the Gly49 variant (thought to be functional), but not variation at Arg389Gly, would be associated with (low) extraversion and shyness. We evaluated the potential for population stratification artifact by genotyping a set of 36 unlinked, highly polymorphic markers previously demonstrated to sufficiently distinguish the ancestry of major American populations. RESULTS: Presence of a Gly49 allele was associated with an increased odds of having low or very low extraversion (odds ratio = 1.68, 95% confidence interval 1.05-2.71). The Arg389Gly polymorphism, although in tight linkage disequilibrium (D' = -1.00) with Ser49Gly, was not significantly associated with level of extraversion. Formal testing showed that population structure did not explain the findings. CONCLUSIONS: The Ser49Gly functional polymorphism in the beta(1) adrenergic receptor might explain some of the population variance in extraversion and related personality traits. Population structure was excluded as an explanation for these findings. We used a sufficient marker set to exclude possible population stratification artifact. These findings should be replicated and extended to the study of psychiatric disorders marked by low extraversion, namely social phobia and other phobic disorders.

Adolescent↗
PubMedDate not supplied

Molecular similarity for small species: refining the isoelectronic index.

This paper tests a chemical-similarity model against properties of gas-phase neutral triatomic and four-atom molecules. The model is a variant of the Diatomics-in-Molecules (DIM) picture, which considers a molecule to be the superposition of all diatomic molecules that could be formed from adjacent atoms in the molecule. The variant is that adjacent atoms are counted as a diatomic molecule only if they are bonded. The tests consist of investigating whether molecules with the same number of electrons, computed by the adjacent-DIM model, have data more similar than do molecules selected at random. The tests vindicate the model for the heat of atomization and for the equilibrium constant for formation, they agree with the model with lesser confidence for the entropy and the partition function, and they show that the model fails for the ionization potential. The model applies with most confidence to molecules with the more electronegative atoms from rows 2 or 3 (those of greatest interest in organic chemistry) and with lesser confidence otherwise. For these properties and these molecules, the model passes graphical and statistical tests at least as well as does the traditional isoelectronic model. Thus, this work refines what may be called the isoelectronic index.

Journal Article↗
PubMed1997

A case-control study of cytochrome P450 1A1, glutathione S-transferase M1, cigarette smoking and lung cancer susceptibility (Massachusetts, United States)

Cytochrome P450 1A1 (CYP1A1) and glutathione S-transferase M1 (GSTM1) genetic polymorphisms are involved in the activation and detoxification of chemical carcinogens found in tobacco smoke; thus they may influence host susceptibility to lung cancer. In this study at Massachusetts General Hospital (Boston, MA, USA) of 416 cases and 446 controls (mostly White) we evaluated the association between the CYP1A1 MspI and GSTM1 polymorphisms and lung cancer risk, and their interaction with cigarette smoke. The CYP1A1 MspI heterozygous genotype was present in 18 percent of cases and 16 percent of controls, and one percent of cases and controls were CYP1A1 MspI homozygous variant. The GSTM1 null genotype was detected in 54 percent of cases and 52 percent of controls. After adjusting for age, gender, pack-years of smoking, and years since quitting smoking, while neither the CYP1A1 MspI heterozygous genotype alone nor the GSTM1 null genotype alone were associated with a significant increase in lung cancer risk, having both genetic traits was associated with a twofold increase in risk (95 percent confidence interval [CI] = 1.0-3.4). Our data did not provide enough evidence for a substantial modification of the effect of pack-years on lung cancer risk by the CYP1A1 MspI and GSTM1 genotypes. However, limitations of our study preclude a conclusion about this potential interaction.

Adult↗
PubMed2003

Interleukin 1alpha, interleukin 1beta and interleukin 1 receptor gene polymorphisms in psoriatic arthritis.

OBJECTIVES: To investigate polymorphisms of interleukin (IL) 1alpha, IL-1beta and IL-1 receptor R1 genes in patients with psoriatic arthritis (PsA), their relationship to the age of onset of psoriasis and the pattern of joint involvement. METHODS: One hundred and forty well-characterized patients with PsA were studied. One hundred healthy controls were recruited from primary care. All were genotyped for single-nucleotide polymorphisms in the genes for IL-1alpha (position -889), IL-1beta (position +3953) and IL-1R1 (position +970). The frequencies of the respective variants were compared between patients and controls and in relation to age of onset of psoriasis, to clinical subsets of the disease and to the presence of erosions. RESULTS: All three polymorphisms were in Hardy-Weinberg equilibrium in both patients and controls. The frequency of IL-1alpha -889 CC homozygotes was significantly increased in PsA patients compared with normal controls [58 vs 40%, odds ratio (OR) 2.06, 95%, confidence interval (CI) 1.22-3.47]. The frequency of the IL-1alpha -889 C allele was significantly increased in PsA patients compared with controls (75 vs 65%, OR 1.65, 95% CI 1.11-2.45). In subset analysis there were no other significant differences in allelic frequencies for the IL-1alpha -889 C/T, IL-1beta +3953 C/T and IL-1R1 +970 C/T polymorphisms. CONCLUSIONS: The IL-1 gene complex may play a role in the development of PsA and/or psoriasis or act as a marker for other genes on chromosome 2q12 to 2q13.

Adult↗