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Multiple risk factors of nasopharyngeal carcinoma: Epstein-Barr virus, malarial infection, cigarette smoking and familial tendency.

A community-based case-control study was carried out to assess multiple risk factors and familial aggregation of nasopharyngeal carcinoma (NPC). All of the 347 pathologically-confirmed NPC new cases were serially recruited from the National Taiwan University Hospital, and healthy community controls one-to-one matched with cases on age, sex and residence were selected from household registration offices. NPC risk factors were obtained from the study subjects through standardized interviews according to a structured questionnaire. Levels of antibody to EBV-specific DNase (anti-EBV DNase) and IgA antibody to EBV viral capsid antigen (anti-EBV VCA) were determined by standard methods blindly. Multiple logistic regression analysis for matched data showed significant associations of NPC with high levels of anti-EBV DNase and anti-EBV VCA independently. The effect of cigarette smoking on NPC was modified by age. The older the age, the more striking the dose-response relation between cigarette smoking and NPC. There was no significant association between alcohol consumption and NPC. Malarial infection history was associated with NPC with an odds ratio of 2.2, but the association was significant in males only. First-degree relatives of NPC cases had a greater NPC-affected rate than those of matched healthy controls with a relative risk of 19.2, and the heritability of NPC was estimated as 0.60 (95% confidence interval = 0.55-0.64) based on the multifactorial inheritance model. Familial NPC cases were younger than sporadic cases, but environmental risk factors were similar in the two groups.

Adult↗
PubMed1990

Osteoarthrosis and congenital dysplasia of the hip in family members of children who have congenital dysplasia of the hip.

Four hundred and eight siblings, parents, and grandparents of seventy-eight children from the New England area who had congenital dysplasia of the hip were evaluated, by clinical examination and by measurements of the acetabulum on pelvic radiographs, for the signs and sequelae of congenital dysplasia of the hip. Six siblings and four mothers (representing seven of seventy-eight families) had been diagnosed with congenital dysplasia of the hip during childhood. The other ninety-one siblings were asymptomatic and had no radiographic evidence of dysplasia of the hip. In the adults in these families, acetabular coverage (as measured by the center-edge angle of Wiberg) was no different from that in the control subjects. There was no difference between the study group and the control subjects in the prevalence of osteoarthrosis of the hip or of osteoarthrosis that could be considered secondary to congenital dysplasia of the hip. The results indicate that children born to families that have a history of congenital dysplasia of the hip have a greater prevalence of this problem compared with the general population, but also that examinations of the hip in newborns are effective in detecting congenital dysplasia of the hip in such families. The greater prevalence of congenital disease of the hip among the siblings and mothers in these families is consistent with a multifactorial inheritance. The fact that acetabular development in the family members who did not have congenital dysplasia of the hip was no different from that in the control subjects suggests that acetabular dysplasia, rather than being an inherited abnormality, is secondary to subluxation or dislocation.

Acetabulum↗
PubMed1989

Evidence for a major additive gene in ulcerative colitis.

Complex segregation analysis of 124 families with ulcerative colitis with two or more affected individuals suggests a rare additive major gene causing the disease with about 20% affected among the heterozygotes for the gene. There was no evidence for multifactorial inheritance.

Colitis, Ulcerative↗
PubMed1989

[Coexistence of porphyria cutanea tarda and lupus erythematosus].

We report on the appearance of porphyria cutanea tarda in a patient with systemic LE and in two patients with discoid LE. A review is given on the corresponding literature. It is suggested that both lupus erythematosus and porphyria cutanea tarda have multifactorial inheritance. The cause of coexistence can be common genes responsible for the genetic determination which also predispose to the occurrence of both diseases. The question of etiology still remains obscure. This coexistence raises, however, a more practical question as regards the therapeutic modalities for the two diseases.

Adult↗
PubMed1988

Closed-angle glaucoma in 20 pairs of twins.

Two pairs of twins with chronic closed-angle glaucoma identified from the Finnish Twin Cohort Study were clinically studied by the author, and 18 other pairs of twins with the disease were ascertained from the Hospital Discharge Registry of Finland. One of the clinically studied pairs was a pair of monozygotic female twins concordant for chronic closed-angle glaucoma and the other was a pair of dizygotic female twins discordant for the disease. Of the pairs of twins ascertained from the registry one was a monozygotic male pair concordant for closed-angle glaucoma. The remaining 17 pairs (12 same-sex dizygotic and 5 monozygotic pairs) were discordant for the disease. The findings support multifactorial inheritance of chronic closed-angle glaucoma.

Aged↗
PubMed1988

Genetic analysis of systemic lupus erythematosus: 1. Detection of disease-associated variant proteins by two-dimensional gel electrophoresis.

Various genetic studies indicate that development of systemic lupus erythematosus (SLE) is regulated by the mode of multifactorial inheritance, i.e., by the overall effect of polygenes and environmental factors. To elucidate some variant genes involved in the polygenic system responsible for onset of SLE, we resolved and measured the protein components of lymphocytes and sera from inactive-SLE patients, their relatives, and normal controls, using two-dimensional gel electrophoresis. Intercomparison of polypeptide patterns between patients and controls revealed three major variations, two detected in lymphocytes and one in sera. These variations were present in 66-82% of the patients, in 20-36% of the control group, and in 41-64% of the relatives. In addition, nearly half of SLE patients, but only one of 19 normal controls, possessed all three SLE-associated traits, suggesting that these variant proteins may reflect in part the genetic factors contributing to development of SLE.

Adolescent↗
PubMed1986

Research for genetic and environmental factors in orthopedic diseases.

This is a review article of the past 40 years of research in Britain on the etiology of developmental disorders of the skeleton, covering both rare unifactorial diseases (chondroosteodystrophies) and common localized disorders (e.g., clubfoot and congenital dislocation of the hip) of multifactorial inheritance.

Bone Diseases, Developmental↗
PubMed1985

[Comparative clinicogenetic study of schizophrenic psychoses].

The author diagnoses 350 carefully selected schizophrenic subjects, their parents and their siblings during parallel studies using three different clinical classification systems and analyzes the results by multiple threshold analysis and the multifactorial inheritance model. The results suggest that, of the three classifications the author studied, Leonhard's and Sneshnewski's system yield relatively homogeneous subgroups; this indicates the future significance of these nosological systems for the planning of biopsychiatric research.

Adult↗
PubMed1984

[Current problems of oncogenetics].

Data available in literature on clinical oncogenetics are reviewed. Pretumour and tumor processes with dominant, recessive and multifactorial inheritance are analyzed in particular. A possibility of application of cytogenetic indices to diagnose initial forms of tumour process and determine the level of anaplasia of developed malignant tumours is suggested. The role of Ukrainian oncologists in oncogenetic studies with the view of comprehending the nature of malignancy and expanding diagnostic possibilities in practical oncology is shown.

Adult↗
PubMed1983

Errors of inference in the detection of major gene effects on psychological test scores.

Computer simulation methods were employed to generate abilities of 10 sets of 250 nuclear families, each comprising a pair of randomly mated parents and two children. It was assumed that the distribution of abilities in the population was normal and caused entirely by additive polygenic effects. A simulated psychological test was administered to each sample to generate test scores for each subject. A different test, consisting of 40 items of varying difficulty and discriminating power, was used in each sample. The "mixed model," specifying a single major gene with polygenic and environmental background variation, was tested for each data set. Likelihood ratios were computed to test for the contribution of a major locus and its conformity to Mendelian segregation. Only one out of 10 samples was consistent with pure multifactorial inheritance. Of the remaining nine samples, four showed non-Mendelian segregation and five were consistent with current statistical criteria for establishing the contribution of a major gene to variation in psychological test scores. This high frequency of false conclusions suggests that the naïve application of such methods to behavioral data is often likely to be misleading. Raw test scores alone are not sufficient to test the mixed model. The development of tractable models for behavioral traits requires the responses of subjects to individual items.

Adult↗
PubMed1983

[Genetic counseling and prenatal diagnosis in families with neural tube defects].

An analysis of 141 families with children with neural-tube defects was performed. The families were consulted in the Department of Genetics, the Institute of Mother and in Child the period between 17.01.1978 and 29.02.1980. The family histories were obtained from the parents. The diagnosis was established on the basis of autopsy data and/or medical records. In cases of multiple congenital malformations coexisting with a neural-tube defect the precise diagnosis of the syndrome was established after a thorough search of the medical literature. Analysis of the material, showed that in 10 families (6,5%) neural-tube defect was associated with other malformations. There were 5 cases of sporadic syndromes (cloacal extrophy-2, aberrant tissue bands-2, sacrococageal teratoma-1), 3 families with Meckel's syndrome and 2 cases in which the nature of the syndrome was not determined. In 131 families the neural-tube defect was isolated and multifactorial inheritance was assumed (table VII). 113 families were given information about the cause of malformation, risk of recurrence, possibility of prenatal diagnosis and indications for amniocentesis (estimation of alpha-foetoprotein in amniotic fluid). After receiving genetic counseling and being fully informed about prenatal diagnosis the parents were asked about their procreative plans and their attitude to amniocentesis. Out of these families 74,3% planned next pregnancy (table IX), 57,6% wanted to have prenatal diagnosis (table VI). 131 family histories (probands with isolated neural-tube defect) were reviewed to determine recurrence risk for relatives. The recurrence risk for sibs was found to be: 4,9% (table III) and was higher than the expected risk (3,4%) from the population incidence of neural-tube defects in Poland (1, 15/1000 births including stillbirths). The recurrence risk for second and third degree relatives was found to be 0,1% (table IV) and 0,3% (table V) respectively.

Adolescent↗
PubMed1982

Genetics of cleft lip and cleft palate in China.

During the past 10 years, 60 cases of cleft lip with or without cleft palate [CL(P)] were recorded among 45,072 newborns at Shanghai International Peace Maternity and Infant Hospital, China. The incidence was 1.33 per 1,000 births. The family histories of 163 CL(P) patients were analyzed. The incidences of CL(P) in the first-, second-, and third-degree relatives of CL(P) patients were 11/246 (4.47%), 10/1,032 (0.97%), and 6/1,727 (0.35%), respectively. Of the 163 probands, three had a history of consanguinity of the parents (1.8%), in contrast to 0.77% in the general population. These data are suggestive of multifactorial inheritance. The heritability of CL(P) in our study calculated by Falconer's formula was 77.6%.

Adult↗
PubMed1981

[Epidemiological study of healthy carriers of Australia antigen. Analysis of contagiousness, and mechanism of spread of the infection (author's transl)].

Epidemiological studies in healthy carriers of HB Ag show variable results that might depend on the geographical area, ethnic group, and socio-economic level analyzed. For that reason an study was undertaken in the Spanish population with the purpose of analysing contagiousness of healthy carriers and mechanism of spread of the infection. The incidence of HB Ag and HB Ab was determined by radioimmunoassay in 211 relatives of 76 healthy carriers; all members of the family could be studied in 51 cases. The results were compared to those of a sizeable sample of the normal population. The overall incidence of HB Ag (13.1 %), and of HB Ab (18.9 %) in the probands was significantly higher than in the normal population (0.8 %, and 9 %, respectively). The distribution of new cases of HB Ag positivity in the 51 families in which the members could be studied demonstrated a significantly higher frequency in children of a carrier mother (28.9 %) than in those of a carrier father (10.8 %). In conclusion, the contagiousness of healthy carriers for their families can not be disregarded. It is likely that the mechanism of spread of the infection depends on a multifactorial inheritance of the genetic alteration of the selective immunologic response to the HB Ag, compounded by environmental factors.

Blood Donors↗
PubMed1980

[Congenital defects of the diaphragm in siblings. Two case reports (author's transl)].

In two different families each time two siblings head a congenital defect of the diaphragm, in 3 cases of the posterolateral type, in 1 case an almost complete aplasia of the diaphragm. Usually, the occurrence of defects of the diaphragm is sporadic. However, familial occurrence has been reported in 15 cases. Multifactorial inheritance is most likely the explanation for this. With this hypothesis a risk of 2% can be calculated for the recurrence of this malformation in a family with already one affected child.

Diaphragm↗
PubMed1977

Familial vesico-ureteral reflux.

Four families of which 2 or more members were affected with primary vesico-ureteral reflux are reported. A multifactorial inheritance pattern subject to environmental factors is likely. Early examination and detection of the disorder in relatives at risk provide an opportunity to avoid the serious sequelae of vesico-ureteral reflux.

Child↗
PubMed1988

[Possibility of the current segregation analysis to discriminate between monogenic and multifactorial types of inheritance of traits. The effect of the structure of family data on model robustness and power of the analysis].

The influence of sampling designs for robustness of the autosomal major locus model and the multifactorial model as well as possibility of segregation analysis to discriminate these models was studied. Nuclear families and 3-generation pedigrees were considered. It was found that robustness of models increased, when the size of sibships in nuclear families grows and when configuration of pedigrees is complicated. The resolution power of the analysis is always increased with size elevation of sibships, the highest effect of the analysis being observed for sibships of the size 3 or 4. Consideration of new generations is only advisable, if attracting sibs of these generations, the resolution power being increased, provided that the parameters of models are of high value.

Genetics, Population↗
PubMed1981

Familial patterns and possible modes of inheritance of primary affective disorders.

A logistic model was used to analyze the pattern of affected relatives of probands with primary affective disorders (PAD). The sample consisted of 242 patients, diagnosed as either unipolar (UP, 107) or bipolar (BP, 135) and 430 control nonpsychiatric inpatients and all first degree relatives of both groups. Age correction was applied to both groups. The analysis showed a significant baseline increase in frequency of PAD among relatives of PAD probands with siblings more likely to be affected than parents. The difference in frequency of PAD according to sex of relative almost reached significance. Specific diagnosis (UP or BP) of proband did not significantly affect the probability of relatives becoming ill. Genetic models incorporating sex-specific thresholds were able to explain the data satisfactorily as resulting from either Single-Major-Locus inheritance or Multifactorial-Polygenic inheritance.

Bipolar Disorder↗