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Results for “Genetic predisposition”

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PubMed1988

Possible genetic predisposition to idiopathic focal segmental glomerulosclerosis.

HLA-A, B, and DR antigen frequencies were studied in a group of 57 patients to determine possible inborn susceptibility to idiopathic focal segmental glomerulosclerosis (FSGS). There were 34 white patients and 23 black patients, most of whom had nephrotic syndrome and later developed renal failure. HLA-DR4 was significantly increased in both patient groups when compared with their respective control groups. This association has not been previously reported. Of note, the association with DR4 was most striking in patients with adult onset disease (in blacks, relative risk equals 5.2; in whites, relative risk equals 5.8). No other antigen was increased in both patient groups but HLA-A28 was increased in blacks. These data support the notion of genetic predisposition to focal segmental glomerulosclerosis in two different ethnic groups.

Adolescent↗

PubMed1997

[Genetic predispositions to breast cancer].

NEW DATA: Genetic epidemiology and position cloning techniques have made it possible to estimate the risk women with a family history of breast cancer have of developing a breast tumor. THREE PREDISPOSITION GENES: Three BReast CAncer genes (BRCA1, BRCA2 and BRCA3) have been localized on chromosomes 17 13 and 8. It is highly likely that other genes also have an influence. GENETIC TESTING: When an altered BRCA1 or BRCA2 gene is identified in a family, a gene test can be proposed to recognize predisposition in relatives. A negative test means the subject is not predisposed to breast cancer and that transmission to offspring is not possible. Inversely, the risk of breast cancer is high if the mutation is detected, raising the difficult problem of counselling, particularly in young subjects. PROBLEMS RELATED TO SCREENING TESTS: Screening tests can only be undertaken if the "candidate" is aware of the consequences of the screening results and has had enough time to make a fully informed decision. Confidentiality must be particularly strict, particularly in the field of employment and insurance.

Breast Neoplasms↗

PubMed1984

Abnormalities in late positive components of event-related potentials may reflect a genetic predisposition to schizophrenia.

Event-related potentials (ERPs) were recorded at the Cz region during syllable discrimination tasks in siblings of schizophrenic probands. ERPs in these siblings were compared to those of normal controls and schizophrenics. Siblings, similar to normal controls, displayed an increase in amplitudes of N100 according to the allocation of their attention between two different channels (ears), Siblings different from normal controls, however, failed to demonstrate an augmentation of late positive components upon detection of target stimuli in the attended channel. Mean amplitudes of late positive components elicited by target stimuli in the attended channel for siblings were nearly equal to those of unmedicated schizophrenics, with these values in siblings being significantly smaller as compared to those of normal controls. Based on these results, it was concluded that abnormalities of late positive components in siblings may reflect a genetic predisposition to schizophrenia.

Adolescent↗

PubMed1994

[Genetic predisposition to latent influenza A virus in children with blood type B(III) as a possible cause of new epidemiologic strains in the countries of South-Eastern Asia].

Regular clinical and epidemiological surveys of two groups of healthy 14-16-year-old boys were carried out for 3 years from September 1989 to May 1992 to investigate the latent circulation of influenza A viruses in the human population. Once or twice a quarter clinical materials were laboratorily studied to detect virus antigens, virus-specific NA-sequences and to determine changes in humoral immunity. The latent circulation of influenza A viruses might be identified in 10-20% of cases long before (2-4 months) the onset of epidemic development. The incidence of epidemic isolations was found to reach 33-36%, gradually decreasing from 29 to 9 or 3.5% in the postepidemic period. The long-term persistence (for 5 months) of virus antigens was reported among healthy children who had chiefly blood group B(III). The new hypothesis that the genetic predisposition of children with blood group B(III) to latent persistence of influenza A viruses may be a possible cause of the emergence of new epidemic strains in the South-East Asian countries has been forwarded.

ABO Blood-Group System↗

PubMed1981

Evidence of genetic predisposition to alcoholic cirrhosis and psychosis: twin concordances for alcoholism and its biological end points by zygosity among male veterans.

Medical histories of the 15,924 male twin pairs in the National Academy of Sciences-National Research Council Twin Registry were examined to determine, within pairs, concordances for alcoholism and its medical end points. Prevalences per 1,000 among individual twin subjects were 29.6 for alcoholism, 4.1 for alcoholic psychosis, 14.2 for liver cirrhosis, and 2.1 for pancreatitis. Prevalences were similar to monozygotic (MZ) and dizygotic (DZ) twins. Prevalences in percent among co-twins of diagnosed subjects, that is case-wise twin concordance rates, were, respectively, by diagnosis: alcoholism: 26.3 (MZ), 11.9 (DZ); alcoholic psychosis: 21.1 (MZ), 6.0 (DZ); and liver cirrhosis: 14.6 (MZ), 5.4 (DZ). No twin pairs concordant for pancreatitis were found. The greater concordance for alcoholic psychosis and for liver cirrhosis among MZ than DZ twins could not be explained by the difference in alcoholism concordance between them. The difference in concordance between MZ and DZ twins persisted when, in addition, it was assumed that only half of the actually occurring cases of alcoholism and of each of the end points have been ascertained. These results provide evidence in favor of genetic predisposition to organ-specific complications of alcoholism and should serve to stimulate searches for the underlying biochemical mechanisms.

Alcoholism↗

PubMed2001

Suicidal behavior: is there a genetic predisposition?

OBJECTIVES: To review the data that support the role of genetic factors in the predisposition to suicidal behavior and to examine whether or not these factors are part of the genetic liability to mood disorders. To review molecular genetic studies carried out in suicidal behavior. METHODS: A review of the literature was carried out by means of systematic bibliographic database searches and complemented by searches in the references of relevant publications. RESULTS: There is consistent evidence suggesting that genetic factors play an important role in the predisposition to suicide and suicidal behaviors. Although there is important overlap between suicide and mood disorders, a common genetic liability seems unlikely. It is possible that part of the predisposition to suicide may be transmitted via the presence of impulsive and impulsive-aggressive behaviors. An increasing number of molecular genetic studies have been carried out in subjects with suicidal behavior. There is some support for a role of some genes that code for components of the serotonergic pathway in the etiology of suicidal behavior, but these studies are still preliminary. CONCLUSIONS: Further studies are needed at the epidemiological, clinical and molecular level to better characterize the genetics of suicide. These should control for the presence of behaviors that are considered as part of the phenotypic spectrum of suicide.

Major Depressive Disorder↗

PubMed1983

Hand eczema in nickel-sensitive female twins. Genetic predisposition and environmental factors.

The Danish Twin Register represents a population-based twin sample where the twins enter the Register independently of disease. All female twins born between 1906-30 and available in the Register in January 1978 were sent a questionnaire concerning possible nickel sensitivity. Among 746 pairs living in the eastern part of Denmark, 129 twins from 115 pairs had a possible nickel allergy. Through a subsequent personal visit and, in most cases, patch testing, 34 monozygotic probands from 30 pairs and 45 dizygotic probands from 41 pairs were considered to have a verified nickel sensitivity and fulfilled the restriction criteria for the present study. The prevalence of present or previous hand eczema in both the monozygotic and the dizygotic probands was 41% (95% confidence limits: 30-52%). In 15 of the 32 with hand eczema, this was in the form of a relapsing pompholyx. Analysis of the monozygotic pairs showed that the risk of developing hand eczema in the co-twins seemed independent of whether the proband had nickel allergy and hand eczema or nickel allergy alone. Furthermore, it was found that the number of affected co-twins was comparable with the background population. Thus the association between nickel allergy and hand eczema is probably not due to a common genetic predisposition. Environmental factors seem decisive.

Aged↗

PubMed2000

Microalbuminuria in never-treated hypertensives: lack of relationship to hyperinsulinemia and genetic predisposition to hypertension.

We evaluated the relationship of microalbuminuria to hyperinsulinemia and family history of hypertension in 92 never-treated essential hypertensives (mean 24-h blood pressure >140 or 90 mm Hg), with positive (F+) or negative (F-) family history of hypertension: 31 had microalbuminuria (MA+) (urinary albumin excretion [UAE], 30 to 300 mg/24 h) and 61 had normal (<30 mg/24 h) UAE (MA-). Glucose and insulin values before and 30, 60, 90, and 120 min after an oral glucose load were measured together with an index of peripheral insulin activity (10(4)/ insulin x glucose values at glucose peak). Subjects with and without microalbuminuria did not differ with regard to age, sex, body mass index, and 24-h heart rate, whereas 24-h, daytime, and nighttime systolic and diastolic blood pressure were significantly higher in MA+ than MA- patients. The prevalence of positive family history of hypertension was similar between MA+ and MA-, as were fasting and stimulated glucose and insulin values and the index of peripheral insulin activity. Subdividing the patients on the basis of family history of hypertension (59 F+, 33 F-) UAE was not significantly different between F+ and F-. UAE did not correlate with glucose and insulin parameters. From our results, in never-treated hypertensives, microalbuminuria is associated with higher blood pressure values, but is related neither to genetic predisposition to hypertension, nor to hyperinsulinemia; therefore, impaired insulin sensitivity and microalbuminuria are two components of the hypertensive syndrome, largely independent of each other.

Adult↗

PubMed1986

Genetic predisposition to liver damage after halothane anesthesia in guinea pigs.

Three 4-hr normoxic (21% oxygen) exposures to 1% halothane administered 3 days apart were associated with elevations in serum alanine aminotransferase (ALT) activity in four of 20 guinea pigs after the initial and third exposures. Serum alanine aminotransferase values were not measured after the second anesthetic. Susceptibility was defined as an ALT level greater than 300 IU/L after halothane. Nonsusceptible animals, that is, animals without significant increases in ALT values after halothane, remained nonsusceptible after reexposure. Serum alanine aminotransferase values after the first and third anesthesias were significantly correlated (rs = 0.86, P less than 0.001). Two exposures of another 30 guinea pigs at a 5-week interval resulted in high elevations of ALT in the same eight animals after both anesthetics. In contrast, after an initial exposure nonsusceptible animals remained nonsusceptible upon reexposure. Serum alanine aminotransferase levels after the first and second anesthetics were significantly correlated (rs = 0.85, P less than 0.001). The proportion of first generation (F1) males with elevated ALTs whose parents were susceptible to halothane hepatotoxicity (HH) was significantly higher than the proportion of males with elevated ALTs in a random group of 90 males (P less than 0.005). First generation males and females of nonsusceptible parents had ALTs within the normal range after halothane exposure. These studies suggest that in the guinea pig genetic predisposition is an important determinant of susceptibility to HH, although other contributing factors are not excluded.

Alanine Transaminase↗

PubMed1985

The adreno-sympathetic system, the genetic predisposition to hypertension, and stress.

The blood pressure, heart rate, and plasma catecholamine (CA) response to standing and mental stresses were studied in 14 normotensive subjects with normotensive parents (PNT group), 14 normotensive subjects with hypertensive parent(s) (PHT group), and eight borderline hypertensive patients (BHT group). Mean basal plasma norepinephrine (NE) concentration in BHT group (302 +/- 94 pg/ml) and PHT group (289 +/- 167 pg/ml) were significantly higher than in PNT group (205 +/- 76 pg/ml). Significant differences in the mean basal plasma epinephrine (E) were found only between the PNT and BHT groups (22 +/- 12 vs 43 +/- 18 pg/ml, p less than 0.01). Both plasma NE and E increased significantly on standing in all groups. With mental stress, plasma E increased significantly, though plasma NE did not change significantly in all three groups. The mean changes in blood pressure, heart rate, and plasma CA in response to standing and mental stresses were not different in the three groups. However, a higher incidence (50%) of high blood pressure responders (greater than or equal to 20 mmHg in systolic blood pressure) to mental stress was found in the PHT group compared with PNT (14%) and BHT (12%). The high responders in the PHT group had significantly higher mean plasma E concentrations throughout the experiment. Also, their increases in plasma NE and E in response to mental stress were higher than those of the low responders. The results indicate that genetic predisposition to hypertension plays a significant role in determining plasma catecholamine levels and the responsiveness to stress, especially to mental stress.

Adolescent↗

PubMed1998

Genetic predisposition to the metabolism of irinotecan (CPT-11). Role of uridine diphosphate glucuronosyltransferase isoform 1A1 in the glucuronidation of its active metabolite (SN-38) in human liver microsomes.

Irinotecan (CPT-11) is a promising antitumor agent, recently approved for use in patients with metastatic colorectal cancer. Its active metabolite, SN-38, is glucuronidated by hepatic uridine diphosphate glucuronosyltransferases (UGTs). The major dose-limiting toxicity of irinotecan therapy is diarrhea, which is believed to be secondary to the biliary excretion of SN-38, the extent of which is determined by SN-38 glucuronidation. The purpose of this study was to identify the specific isoform of UGT involved in SN-38 glucuronidation. In vitro glucuronidation of SN-38 was screened in hepatic microsomes from normal rats (n = 4), normal humans (n = 25), Gunn rats (n = 3), and patients (n = 4) with Crigler-Najjar type I (CN-I) syndrome. A wide intersubject variability in in vitro SN-38 glucuronide formation rates was found in humans. Gunn rats and CN-I patients lacked SN-38 glucuronidating activity, indicating the role of UGT1 isoform in SN-38 glucuronidation. A significant correlation was observed between SN-38 and bilirubin glucuronidation (r = 0.89; P = 0.001), whereas there was a poor relationship between para-nitrophenol and SN-38 glucuronidation (r = 0.08; P = 0.703). Intact SN-38 glucuronidation was observed only in HK293 cells transfected with the UGT1A1 isozyme. These results demonstrate that UGT1A1 is the isoform responsible for SN-38 glucuronidation. These findings indicate a genetic predisposition to the metabolism of irinotecan, suggesting that patients with low UGT1A1 activity, such as those with Gilbert's syndrome, may be at an increased risk for irinotecan toxicity.

Animals↗

PubMed2006

Familial genetic predisposition, epilepsy localization and antecedent febrile seizures.

PURPOSE: The magnitude of genetic influence in epilepsy may vary in relation to epilepsy classification and localization and factors such as antecedent febrile seizures. We assessed this genetic influence in a large epilepsy population. METHODS: Patients with established epilepsy diagnosis evaluated in the Vanderbilt Epilepsy Program were systematically questioned about family history of epilepsy and febrile seizures, prior febrile seizures and other risk factors for epilepsy. RESULTS: A total of 1994 patients with epilepsy and reliable family history were identified. Patients with prior febrile seizures (FS) were more likely to have a family history of febrile seizures than those without prior FS (p<0.000001) and also had a greater proportion of relatives with febrile seizures. The groups did not differ with respect to family history of epilepsy. Patients with generalized epilepsy were more likely to have first and second degree relatives with epilepsy than those with partial epilepsy (40.2% versus 31.2%, p=0.001), and also had a greater proportion of affected first degree relatives (p<0.000001). The proportion of first degree relatives affected with epilepsy was higher than local published prevalence, for both groups. CONCLUSION: Susceptibility for febrile seizures with subsequent epilepsy may be genetically distinct from susceptibility for afebrile seizures alone. Although family history of epilepsy was more likely with generalized epilepsy, a familial tendency was considerable in partial epilepsy.

Adolescent↗

PubMed1999

Genetic predisposition to skin cancer.

Here we review recent insights in the genetics of skin cancer susceptibility as gleaned from studies of three hereditary syndromes: basal cell nevus syndrome, familial melanoma/dysplastic nevus syndrome, and xeroderma pigmentosum. We provide a brief synopsis of the recent findings related to these syndromes in an attempt to illustrate several emerging themes in the genetics of skin cancer. These themes include 1) the recent identification of multiple cancer susceptibility genes that occur in a myriad of cellular regulatory pathways; 2) the relative specificity of certain regulatory pathways to the development of specific types of cancer; and 3) the important role of DNA damage caused by ultraviolet radiation and defective DNA repair mechanisms in the development of skin cancer. We also review the implications of this knowledge to clinical practice relative to risk assessment, primary prevention, and therapy.

Basal Cell Nevus Syndrome↗

PubMed2000

Genetic predisposition to stroke in relatives of hypertensives.

BACKGROUND AND PURPOSE: The genetic basis of stroke is poorly understood. We evaluated patterns of familial aggregation of hypertension and stroke to test the hypothesis that inherited susceptibility to these disorders may be determined by a common set of factors. METHODS: Genealogical and medical history information was obtained for a cohort of 354 hypertensive probands ascertained in a clinic-based setting, their 1427 first-degree relatives, and 239 of their spouses. Risks of stroke and hypertension in biological and nonbiological relatives were compared with the logistic model of the generalized estimating equations adjusted for age and sex. RESULTS: The risk of hypertension was higher for the parents and siblings of the probands than for spouses (odds ratio [OR]=2.4; 95% CI, 1.8 to 3.4; OR=2.2; 95% CI, 1.6 to 3.0, respectively). When the spouses were used as a reference group, the risk of stroke for parents of the hypertensive probands was 7.3 times higher (OR=7.3; 95% CI, 3.6 to 14.8), while a nonsignificant but slightly increased risk for siblings (OR=1.6; 95% CI, 0.8 to 3.3) was observed. Controlling for hypertension, obesity, smoking, coronary heart disease, diabetes, and cholesterol resulted in decreased estimates of the risk of stroke for parents and siblings (OR(parents)=5.4; 95% CI, 2.6 to 11.2; OR(siblings)=1.2; 95% CI, 0.6 to 2.5). The risk of stroke was significantly higher for hypertensive parents and siblings than for nonhypertensive parents (OR=5.2; 95% CI, 2.8 to 9. 7) and siblings (OR=5.8; 95% CI, 2.1 to 15.9). A history of hypertension was not associated with an increased risk for stroke in spouses (OR=0.7; 95% CI, 0.2 to 3.1). The risk of stroke in hypertensive relatives of probands with stroke was higher than that of the normotensive relatives (OR=13.4). A less elevated risk ratio was observed in the relatives of probands who did not have a stroke (OR=4.0). CONCLUSIONS: Our data showing a higher occurrence of hypertension and stroke in parents of hypertensive probands compared with spouses suggest that some of the genetic factors predisposing to these conditions may be the same. The slightly increased risk to siblings compared with spouses was not significant, suggesting that elucidation of these factors through family studies of stroke may be difficult because of secular trends toward improved treatment for hypertension. Although a history of hypertension increases the risk of stroke among parents and siblings, multivariate analyses revealed a familial component to stroke independent of hypertension.

Aged↗

PubMed2004

Familial hypercholesterolemia: genetic predisposition to atherosclerosis.

Familial hypercholesterolemia is one of the most frequent genetic disorders. The increased cholesterol levels in the plasma low-density lipoprotein fraction due to the diminished number or absence of LDL receptors predispose affected individuals to premature atherosclerosis and cardiovascular disease.

Arteriosclerosis↗

PubMed1998

Effects of genetic predisposition on proinsulin responses in Asian Indians.

This study was done in adult offspring of two diabetic (NIDDM) parents (ODP) to look for changes in specific insulin (insulin) and proinsulin responses due to strong familial background and also in different states of glucose intolerance. Equal numbers (20 in each group) of ODP with normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and diabetes (DM) were chosen. Twenty, age and BMI matched healthy controls, without family history of diabetes, were also studied for comparison. Plasma specific insulin and proinsulin were measured by radioimmunoassays in fasting and 120' plasma samples collected during the GTT. Proinsulin to insulin ratio were calculated. Insulin resistance (IR-HOMA) was calculated. In NGT, fasting proinsulin-insulin ratio was significantly higher than the control value (P = 0.023). Insulin values at 120' was higher than control values, though it did not reach statistical significance. Proinsulin at 120' was higher than controls (P = 0.016). In IGT, the fasting proinsulin to insulin ratio, the 120' proinsulin and insulin values were higher than controls (P = 0.048, 0.0013 and 0.0001, respectively). Fasting proinsulin-insulin ratio in IGT was similar to the value in NGT. In diabetic subjects proinsulin concentrations were significantly higher than controls at fasting (P = 0.0004), and 120' (P = 0.0007). The fasting values were higher compared to NGT also (P = 0.037). Proinsulin-insulin ratios were higher than the values in controls (P = 0.0008), IGT (P = 0.047) and NGT (P = 0.05). Diabetic subjects had higher fasting insulin values compared to the control values although between the groups no statistical significance was found (P = 0.22 by Kruscall Wallis test). At 120' both insulin and proinsulin values increased from NGT to IGT, but with development of diabetes a reduction was seen in the responses. Insulin resistance (IR-HOMA) increased steadily from NGT to diabetes. The difference between NGT and controls in IR was not statistically significant. This study of Asian Indian offspring of diabetic parents has shown that genetic predisposition to diabetes resulted in increased proinsulin to insulin ratio at the fasting state. Absolute hyperproinsulinaemia occurred only with development of diabetes.

Adult↗

PubMed2026

Familial lymphoma and genetic predisposition: an updated review.

BACKGROUND: Several factors contribute to the development of malignant lymphomas including environmental exposures, bacterial and viral infections, as well as familial and genetic factors. MAIN BODY: Numerous somatic variants are involved in lymphomagenesis, and an increasing number of germline variants predisposing patients to lymphoid neoplasm have been identified. Although most lymphomas arise sporadically, epidemiological studies have linked a familial history of lymphomas and other hematological tumors with an increased lymphoma risk. Although rare, familial clustering of malignant lymphoma is well documented, and the constellations suggest inherited risk factors. Recent technological advancements have improved our ability to identify genetic factors associated with lymphoma that overall lead to a better understanding of genetic susceptibility for these entities. In this context, we here provide a comprehensive perspective on lymphoma risk factors to support improved lymphoma risk assessment and testing. A dedicated clinical management could influence future advances in lymphoma therapies and might also prevent severe toxicity and secondary malignancies. However, to date, only few susceptibility genes for malignant lymphomas have been identified. Highly penetrant mutations in known genes cannot account for most of the excess in a polygenic and heterogenic disease such as cancer. High-throughput sequencing identifies pathogenic variants that may constitute most low-penetrance alleles. However, their detection requires many well-characterized cases and controls. In this review, we therefore also include a short discussion on a Swiss cohort where we prospectively collect and samples for genetic data from individuals with a family history of lymphoma. We are convinced that such an approach is more informative and feasible than a population-based project with unselected cases and aim to better inform both genetic counsellors and oncologists. CONCLUSION: Inherited genetic factors contribute to lymphoma risk in a subset of patients. Improved identification of susceptibility variants, particularly through family-based studies, may enhance risk assessment and inform personalized clinical management.

Humans↗

PubMed2001

TNFRSF1B in genetic predisposition to clinical neuropathy and effect on HDL cholesterol and glycosylated hemoglobin in type 2 diabetes.

OBJECTIVE: Genetic variation in the tumor necrosis factor (TNF) receptor 2 gene (TNFRSF1B) has shown association with insulin resistance in type 2 diabetes, hypercholesterolemia, coronary artery disease, and essential hypertension. Here we tested the TNFRSF1B marker used in the latter studies in type 2 diabetes patients. RESEARCH DESIGN AND METHODS: A case-control study of a microsatellite marker with five alleles (CA13- CA17) in intron 4 of TNFRSF1B was performed in 357 well-characterized white patients and 183 healthy control subjects. RESULTS: The CA16 allele was associated with clinical neuropathy (frequency = 27% in 69 patients with the condition versus 16% in 230 subjects without the condition; chi2 = 9.0, P = 0.011; odds ratio = 2.1 [95% CI 1.2-3.8]). No association was seen with other complications or diabetes itself. The CA16 allele tracked with elevation plasma HDL cholesterol (1.3 +/- 0.2, 1.2 +/- 0.4, and 1.1 +/- 0.2 for CA16/CA16, CA16/-, and -/-, respectively; n = 9, 110, and 218, respectively; P = 0.009) and reduction in plasma glycosylated hemoglobin (6.6 +/- 0.3, 8.3 +/- 0.2, and 8.1 +/- 0.1 for CA16/CA16, CA16/-, and -/-, respectively; n = 9, 102, 205, respectively; P = 0.007) Significance remained after Bonferroni correction for multiple testing. CONCLUSIONS: Genetic variation in or near TNFRSF1B may predispose clinical neuropathy, reduced glycosylated hemoglobin, and increased HDL cholesterol in type 2 diabetes patients. The latter could be part of a protective response.

Aged↗