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At least 19 recordsLinked to original sources
PubMed1993

Severity differences in beta-thalassaemia/haemoglobin E syndromes: implication of genetic factors.

Genetic factors determining the difference in severity of anaemia in beta-thalassaemia/HbE disease were studied in 90 patients who had haemoglobin levels, at steady state, ranging from 4.2 to 12.6 g/dl. Co-inheritance of alpha-thalassaemia 2 and haemoglobin Constant Spring could significantly decrease the severity of the disease. Inheritance of a beta-thalassaemia chromosome with Xmn I cleavage site at position -158 of the G gamma-globin gene which was linked to the haplotype -+-++ or ++-++, was associated with a milder anaemia. Two copies of these alleles were necessary to produce a significant clinical effect. Increased expression of the G gamma-globin gene and higher production of haemoglobin F, which could reduce the overall globin chain imbalance, were also associated with homozygosity for the Xmn I cleavage site and thus with less severe anaemia. However, this effect was not seen in Xmn I site heterozygotes. Whether the effects of the Xmn I polymorphism, HbF concentration and G gamma/A gamma ratio act separately or through common mechanisms in reducing anaemia remains to be ascertained.

Adolescent↗
PubMed2003

[Epidemiology of multiple sclerosis: environmental factors versus genetic factors].

Although the mechanism of multiple sclerosis (MS) remains elusive, it is generally hypothesized to be an autoimmune disease targeting the central nervous system (CNS) myelin. Extensive epidemiological and genetic surveys indicate that MS is caused by an interplay between the environment and genetic traits determined by normal polymorphisms in multiple genes. In Japanese, epidemiological surveys gave the prevalence rates of 0.7 to 8.9/100,000. There is a small but significant north-to-south gradient of MS prevalence rates in Japan, suggesting that environmental factors varying with latitude also play a role in developing MS even in the low prevalence areas. Conventional MS in Japanese is, like MS in Caucasians, associated with HLA-DRB1*1501 whereas opticospinal MS is associated with HLA-DPB1*0501. The ratio of conventional to opticospinal MS has increased rapidly in Japanese born after 1960s, suggesting that the modernization occurred after 1960s in Japan has modifying effects on MS susceptibility and phenotypes.

Diseases in Twins↗
PubMed1999

Carcinogenesis in the colon: interaction between luminal factors and genetic factors.

At last, inroads are beginning to be made into the hitherto unknown and complex area of gene-environment interactions in the colon. Interestingly, many of the studies to date would suggest: that the Apc gene is a target for such interactions; that luminal factors can regulate the level of cellular proteins of central importance in the control of cell growth/arrest; and that some of the newly discovered members of the nuclear hormone receptor superfamily may be mediating gene-environment interactions in the colon. This is a very exciting area and will presumably be the subject of intense research in the near future. By characterizing the dietary/luminal factors that interact with the genes implicated in tumour development in the colon, we will reach another level of certainty regarding the dietary components responsible for tumour formation and their underlying mechanisms. It is gratifying to see at last the fields of epidemiology and molecular biology begin to overlap, and without doubt results from this new area of research will give a new and better status to the field of making dietary recommendations to decrease the risk of developing colorectal cancer.

Animals↗
PubMed2004

GENETIC FACTORS IN EXTERNAL APICAL ROOT RESORPTION AND ORTHODONTIC TREATMENT.

External apical root resorption (EARR) is a common sequela of orthodontic treatment, although it may also occur in the absence of orthodontic treatment. The degree and severity of EARR associated with orthodontic treatment are multifactorial, involving host and environmental factors. Genetic factors account for at least 50% of the variation in EARR. Variation in the Interleukin 1 beta gene in orthodontically treated individuals accounts for 15% of the variation in EARR. Historical and contemporary evidence implicates injury to the periodontal ligament and supporting structures at the site of root compression following the application of orthodontic force as the earliest event leading to EARR. Decreased IL-1beta production in the case of IL-1B (+3953) allele 1 may result in relatively less catabolic bone modeling (resorption) at the cortical bone interface with the PDL, which may result in prolonged stress concentrated in the root of the tooth, triggering a cascade of fatigue-related events leading to root resorption. One mechanism of action for EARR may be mediated through impairment of alveolar resorption, resulting in prolonged stress and strain of the adjacent tooth root due to dynamic functional loads. Future estimation of susceptibility to EARR will likely require the analysis of a suite of genes, root morphology, skeleto-dental values, and the treatment method to be used-or essentially the amount of tooth movement planned for treatment.

Journal Article↗
PubMed2005

Effects of dietary intake and genetic factors on hypermethylation of the hMLH1 gene promoter in gastric cancer.

AIM: Hypermethylation of the promoter of the hMLH1 gene, which plays an important role in mismatch repair during DNA replication, occurs in more than 30% of human gastric cancer tissues. The purpose of this study was to investigate the effects of environmental factors, genetic polymorphisms of major metabolic enzymes, and microsatellite instability on hypermethylation of the promoter of the hMLH1 gene in gastric cancer. METHODS: Data were obtained from a hospital-based, case-control study of gastric cancer. One hundred and ten gastric cancer patients and 220 age- and sex-matched control patients completed a structured questionnaire regarding their exposure to environmental risk factors. Hypermethylation of the hMLH1 gene promoter, polymorphisms of the GSTM1, GSTT1, CYP1A1, CYP2E1, ALDH2 and L-myc genes, microsatellite instability and mutations of p53 and Ki-ras genes were investigated. RESULTS: Both smoking and alcohol consumption were associated with a higher risk of gastric cancer with hypermethylation of the hMLH1 gene promoter. High intake of vegetables and low intake of potato were associated with increased likelihood of gastric cancer with hypermethylation of the hMLH1 gene promoter. Genetic polymorphisms of the GSTM1, GSTT1, CYP1A1, CYP2E1, ALDH2, and L-myc genes were not significantly associated with the risk of gastric cancer either with or without hypermethylation in the promoter of the hMLH1 gene. Hypermethylation of the hMLH1 promoter was significantly associated with microsatellite instability (MSI): 10 of the 14 (71.4%) MSI-positive tumors showed hypermethylation, whereas 28 of 94 (29.8%) the MSI-negative tumors were hypermethylated at the hMLH1 promoter region. Hypermethylation of the hMLH1 gene promoter was significantly inversely correlated with mutation of the p53 gene. CONCLUSION: These results suggest that cigarette smoking and alcohol consumption may influence the development of hMLH1-positive gastric cancer. Most dietary factors and polymorphisms of GSTM1, GSTT1, CYP1A1, CYP2E1, ALDH2, and L-myc genes are not independent risk factors for gastric cancer with hypermethylation of the hMLH1 promoter. These data also suggest that there could be two or more different molecular pathways in the development of gastric cancer, perhaps involving tumor suppression mechanisms or DNA mismatch repair.

Adaptor Proteins, Signal Transducing↗
PubMedDate not supplied

Familial systemic sclerosis following exposure to organic solvents and the possible implication of genetic factors.

Both genetic and environmental factors are suspected to play a role in the pathogenesis of systemic sclerosis. We compare its occurrence in 3 sisters working in a dry cleaner's shop and exposed to occupational inhalation of organic solvents. Two sisters showing the human leukocyte antigens (HLA)-DR11/DQ7 haplotype were affected. The third has maintained the same job as the others for over 10 years and has no signs of the disease. The fact that she has a different HLA haplotype points to the significance of genetic factors in increasing the risk of systemic sclerosis. It is suggested that the DR11/DQ7 haplotype enhances the development of a clinical subset of systemic sclerosis associated with production of anti-topoisomerase-I antibodies, and that environmental triggers prime the disease in subjects with this genetic background.

Female↗
PubMed1994

Genetic factors in alcohol use-a genetic epidemiological perspective.

The purpose of this paper is to put a genetic epidemiological perspective on the role of genetic factors involved in the susceptibility and expression of alcohol use. The consequences of familial aggregation in a trait is explained, and the evidence for familial aggregation in alcoholism is viewed critically. Methods for making inference about unmeasured genetic factors from family-based studies of twins, adoptees, etc. are examined. The meaning and limitations of "heritability" are explained. A summary of the literature regarding the possible role of genetic factors on several aspects of alcohol use, including alcohol metabolism, is presented. Some of the evidence for measured genetic factors related to alcoholism and alcohol use is examined. The basic requirements for justifying genetic screening for an adult onset condition, such as alcoholism, are outlined. It is concluded that, although behavioural geneticists have tended to overstate the case for a genetic aetiology, it may only be a matter of time before one or more genetic loci, which in some part determine susceptibility to problem drinking and alcohol abuse, are identified. Genetic screening programmes, however, are unlikely to be justified, especially given the lack of proven prevention strategies.

Journal Article↗
PubMed2005

Variation in plasma insulin-like growth factor-1 and insulin-like growth factor binding protein-3: genetic factors.

Insulin-like growth factors (IGFs) play key roles in cell proliferation and apoptosis. Whereas relatively stable within individuals, IGFs vary substantially between individuals, and a large component of this variation may be determined by genetic factors. Several polymorphisms in IGF genes have been identified, although their functional significance is not clear. We evaluated the association of polymorphisms in IGF-1 and IGFBP-3 and circulating levels of IGF-1 and IGFBP-3 in 323 population-based control subjects enrolled in a case-control study of colorectal cancer from September 1999 through February 2002. Total IGF-1 and IGFBP-3 levels were measured using ELISA assays, and all subjects were genotyped for a microsatellite polymorphism in IGF-1 and a single nucleotide polymorphism in IGFBP-3. Multiple linear regression was used to assess the association of genotype with circulating IGFs. IGF-1 levels were unrelated to either polymorphism. IGFBP-3 was significantly associated with IGFBP-3 genotype, with IGFBP-3 levels increasing from CC (1,895 ng/mL) --> GC (2,029 ng/mL) --> GG (2,182 ng/mL), (p-trend < 0.001). Having an IGF-1 genotype other than homozygous for the 19-repeat allele was associated with higher IGFBP-3 levels (1,945 versus 2,052 ng/mL). Furthermore, both IGF-1 and IGFBP-3 genotypes modified the relationship between postmenopausal hormone use and IGFs. This analysis provides evidence that common variation in IGF genes may contribute to the variation in circulating levels observed between individuals.

Adult↗
PubMed1998

[Current opinions on the etiology and pathogenesis of autosomal dominant polycystic kidney disease (ADPKD). II. Factors other than genetic factors which have an influence on disease course and selected clinical problems].

In the first part of this paper achievements in the genetic investigations of ADPKD and pathomechanism of cyst formation have been presented. Majority of authors acknowledge that first type of the disease (ADPKD1) in comparison with the second (ADPKD2) has more severe clinical course. On the basis of clinical analysis of selected affected families the larger and larger emphasis has been put on the influence of such factors like: presence of arterial hypertension, especially role of RAA system, sex, diet, hyperlipoproteinemia, environmental factors, toxic and infectious agents. It seems that genetic analysis of the RAA system and ADPKD will partially explain differences in the clinical course of the disease in different families. Persons with DD genotype in RAA system have statistically significant, more severe clinical course in comparison with their relatives with DI or II genotype. Decidedly worse course of the disease is observed in patients with positive family history of arterial hypertension and in persons with increased blood pressure. Patients sex play a major role. Men have more severe renal manifestations, when in women symptoms and complications associated with liver cysts are more frequent than in men. Frequency of intracranial aneurysms (ICA) in the population of patients with ADPKD have been presented. CT, MRA and classical angiography are in order screening tests for detection of ICA, especially in persons with family history of their prevalence. Prevalence of liver cysts and selected clinical symptoms and complications associated with extrarenal manifestations have been discussed. Problems associated with infections of the urinary tract and cysts, their etiology, pathomechanisms and treatment have been presented. Ultrasonography seems to be the best diagnostic tool because of it's accessibility, high sensitivity and low cost. It is accepted, that presence of 3 cysts in both kidneys in ADPKD kindreds in significant for diagnosis. Modified Ravine's criteria for diagnosis of ADPKD have also been presented. Employment of modern diagnostic methods in combination with genetic analysis (especially linkage analysis) enable early diagnosis in persons who are at risk of ADPKD.

Comorbidity↗
PubMed2005

[From the sociological factor to the genetic factor. Genes and disease in the pages of El País (1976-2002)].

Transformations in the Spanish public discourse on the link between genes and disease are analysed by an attentive reading of the journalistic texts published in El País between 1976 and 2002, and the newspaper's model of popularisation is explored. Whereas in the seventies a social and complex vision of disease was favoured, by the nineties the genetic approach was predominant. El País supported this "geneticisation" and forested an increasingly neutral and apolitical image of science.

Disease↗
PubMedDate not supplied

Epileptic seizures and syndromes in twins: the importance of genetic factors.

The role of genetic factors in the occurrence of epilepsy syndromes was studied in twins recruited from the population-based Danish Twin Registry. A total of 34,076 twins were screened for epilepsy. Cases were confirmed and classified by two neurologists according to the classification systems of the International League Against Epilepsy (ILAE). A total of 214 twin pairs with epileptic seizures and 190 pairs with epilepsy were ascertained. Significantly higher concordance rates were found for monozygotic (MZ) compared to dizygotic (DZ) twins for both epileptic seizures (0.56 for MZ and 0.21 for DZ pairs, P<0.001) and for epilepsy (0.49 for MZ and 0.16 for DZ pairs, P<0.001). Concordance rates were also higher for MZ twins compared to DZ twins for both generalized epilepsy (0.65 for MZ and 0.12 for DZ) and for localization-related epilepsy (0.30 for MZ and 0.10 for DZ). In twin pairs where both members had seizures, 83% of MZ and 65% of DZ pairs had the same major epilepsy syndrome. Genetic factors were found to account for 80% of the liability to both epileptic seizures and epilepsy. In conclusion, analysis of this neurologist-verified epilepsy twin data set has confirmed that genetic factors have a substantial impact on the etiology of epileptic seizures as well as on the occurrence of both generalized and partial epilepsies.

Adolescent↗
PubMed1999

Factor XIII Val34Leu is a genetic factor involved in the etiology of venous thrombosis.

A mutation in the factor XIII gene (FXIII Val34Leu) gene was recently reported to confer protection against myocardial infarction, but its relationship with venous thrombosis is unknown. In addition, a mutation in the 5'-untranslated region of the FXII gene (46 C->T) was identified which is associated with low plasma levels of the protein. Its prevalence in patients with venous thrombosis is also unknown. We investigated the frequency of the FXIII Val34Leu and FXII 46 C->T mutations in 189 patients with deep venous thrombosis and in 187 age-, gender- and race-matched controls. FXIII Val34Leu was detected in 38.6% of the patients and in 41.2% of the controls. Interestingly, homozygosity for the FXIII mutation was found in 1.6% of the patients and in 9.6% of the controls, yielding an odds ratio (OR) for venous thrombosis of 0.16 (95% CI: 0.05-0.5). The OR for heterozygotes was 1.1 (95% CI: 0.7-1.7). The FXII 46 C->T mutation was detected in 46.0% of the patients and in 48.6% of the controls. The OR for heterozygotes was 0.9 (95% CI: 0.6-1.4) and for homozygotes the OR was 0.8 (95% CI: 0.3-1.9). Our data indicate that the FXII 46 C->T mutation is unlikely to be a major risk factor for venous thrombotic disease. In contrast, the homozygous state for FXIII Val34Leu is a strong protective factor against venous thrombosis, which emerges as a novel genetic factor involved in the aetiology of thrombophilia.

Adolescent↗
PubMed1991

Genetic factors in bone turnover.

Genetic factors are major determinants of adult bone density, however, it is unknown how these effects may be mediated. Since bone mineral density is the net result of bone formation and bone resorption we studied biochemical indices of bone formation (serum osteocalcin) and resorption [fasting urinary calcium:creatinine (Ca/Crt) and hydroxyproline:creatinine (OH/Crt)] in adult female twins; 39 monozygotic (MZ) and 31 dizygotic (DZ) twin pairs (age, mean +/- SEM, MZ: 51.1 +/- 1.5 yrs; DZ: 46.5 +/- 1.5 yrs, P = NS). Of these subjects, 18 MZ twin pairs and 10 DZ twin pairs were postmenopausal. The MZ twin pair correlations (rMZ) for each index of bone turnover exceeded that between DZ pairs (rDZ), but this difference was only significant for osteocalcin (rMZ = 0.81, rDZ = 0.21, P less than 0.001). Similarly, in the postmenopausal group examined alone, the rMZ (r = 0.84) for serum osteocalcin was significantly greater than rDZ (r = -0.003, P less than 0.03). These osteocalcin data imply that 80% of the variance in serum osteocalcin could be explained by genetic factors. Although genetic effects on fasting urinary hydroxyproline:creatine and calcium:creatinine were not demonstrable, these indices may be less precise and specific. The data indicate that circulating osteocalcin, and therefore bone formation, is strongly genetically determined. These studies suggest at least one of the mechanisms of the genetic effect on bone mass relates to the regulation of bone turnover.

Adult↗
PubMed2001

Silent stroke: pathogenesis, genetic factors and clinical implications as a risk factor.

Silent stroke is frequently recognized in elderly persons. Diffusion-weighted magnetic resonance imaging has proved to be highly sensitive in the detection of recent silent stroke, and may further applications in the future. Silent stroke in healthy and asymptomatic individuals mainly comprises lacunar infarcts, which are often associated with white matter changes. Thus, analyses of risk factors and genetic factors in small-vessel diseases such as lacunar infarct and white matter changes may provide clues regarding the pathogenesis of silent stroke. Silent stroke may be a risk factor for clinical stroke and cognitive impairment, but prospective studies are required to confirm this.

Genetic Predisposition to Disease↗