• Tuberculosis and Respiratory Diseases
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• v.44 no.3
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• pp.534-546
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• 1997

Background : The p53 and retinoblastoma(Rb) tumor suppressor genes are associated with the pathogenesis of several types of human cancer. Substantial proportion of the primary lung cancers or cell lines have been reported to have the p53 and/or the Rb gene mutations. But, so far there is no report on the analysis of the Rb gene polymorphism as one of the genetic susceptibility marker. This study was undertaken to establish the gene frequencies of the polymorphic genotypes of the p53 and Rb genes in Koreans to evaluate the possible involvement of these genotypes as a risk factor of lung cancer. Methods : In this study 145 controls without previous and present tumor history and 128 lung cancer patients were subjected to analysis. The two intragenic polymorphisms of the p53 gene(exon 4/ AccII, intron 6/MspI) and one intron 17/XbaI polymorphism of the Rb gene were analysed by the method of polymersae chain reaction- restriction fragment length polymorphisms(PCR-RFLPs). The genotype of the intron 3/16 bp repeat polymorphism of p53 was determined by PCR and direct gel electrophoresis. Results : There were no significant differences in the genotype distributions of the p53 gene between lung cancer patients and controls. But heterozygotes(Arg/Pro) of the exon 4/AccII polymorphisms were slightly over-represented than controls, especially in the Kreyberg type I cancer, which was known to be associated with smoking. The intron 3/16 bp duplication and the intron 6/MspI polymorphisms were in complete linkage disequilibrium. About 95% of the individuals were homozygotes of the common alleles both in the 16 duplication and MspI polymorphisms, and no differences were deteced in the genotype distributions between lung cancer patients and controls. Overall genotype distributions of the Rb gene polymorphisms between lung cancer patients and controls were not significantly different However, the genotype distributions in the Kreyberg type I cancer were significantly different from those of controls(p = 0.0297) or adenocarcinomas(p = 0.0008). It was noticeable that 73.4% of the patients with adenocarcinomas were heterozygotes(r1/r2) whereas 39.2% of the Kreyberg type I cancer were heterozygous at this polymorphisms. In the lung cancer patients, significant differences were also noted between the high dose smokers and low dose smokers including non-smokers(p = 0.0258). The relative risk to Kreyberg type I cancer was significantly reduced in the individuals with the genotype of r1/r2(odds ratio = 0.46, 95% C.I. = 0.25-0.86, p = 0.0124). The combined genotype distribution of the exon 4 AccII of the p53 and the intron 17 Rb gene polymorphisms in Kreyberg type I cancers were significantly different from dose of controls or adenocarcinomas. The highest odds ratio were observed in the individuals with the genotypes of Arg/Pro and r2/r2(odds ratio = 1.97,95% C.I. = 0.84-4.59) and lowest one was in the patients with Arg/Arg, r1/r2 genotype(odds ratio = 0.54, 95% C.I. = 0.25-1.14). Conclusion : The p53 and the Rb gene polymorphisms modulate the risk of smoking induced lung cancer development in Koeans. However, the exact mechanism of risk modulation by these polymorphism remains to be determined. For more discrete clarification of associations between specific genotypes and lung cancer risk, the evaluations of these polymorphisms in other ethnics and more number of patients will be needed.

• Childhood Kidney Diseases
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• v.9 no.2
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• pp.222-230
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• 2005

Purpose : ARC syndrome refers to an association of arthrogryposis, renal tubular dysfunction, and cholestasis. The VPS33B gene was recently identified as the causative gene. So far, 41 cases of ARC syndrome have been reported worldwide, and it has rarely been reported in Korea. This study was conducted to report the clinical findings of seven ARC syndrome cases in Korean children, focusing especially on renal tubular dysfunction. Methods : The hospital records of 7 cases diagnosed as ARC syndrome at Severance Hospital between Mar. 1995 and Aug. 2005 were reviewed and analyzed. Results : Of the 7 cases, 4 were boys and 3 were girls. Six patients(85$\%$) were born with normal birth weight at term, and one was born at preterm. All cases presented with cholestasis and severe jaundice. According to the type of arthrogryposis described by Brown et al, type 3 and 4 were found in 2 patients and type,6, 7, and the undistributed type in one patient respectively. Other associated clinical findings were as follows : failure to thrive in 6(85$\%$), lax skin in 5(71$\%$), and gray platelet syndrome in 4(57$\%$). Urine analysis revealed 6 cases(85$\%$) with proteinuria, 3(43$\%$) with hematuria, 5(71$\%$) with glycosuria, 2(29$\%$) with phosphaturia and 2(29$\%$) with calciuria. Serum electrolytes showed 4 cases(57$\%$) with hyponatremia, 3(43$\%$) with hypokalemia, and 1(14$\%$) with creatinine elevation. Renal tubular dysfunctions were diagnosed as renal tubular acidosis in 6 cases(85$\%$), nephrogenic diabetes insipidus in 2(29$\%$), and Fanconi syndrome in 2(29$\%$). During the follow-up period, 2(29$\%$) had no treatment, 5(85$\%$) had continuous supplementation to correct the electrolyte imbalance and acidosis, and 1(14$\%$) had dialysis. Only one patient had a family history of ARE syndrome in a sibling. Four cases(57$\%$) were diagnosed at the mean age of 8.2 months, and one case was lost during follow-up. Ages of the survived 2 cases were 13 and 25 months, respectively. Conclusion : The rare disease of ARC syndrome Is associated with severe renal dysfunction. However, this study revealed that the renal manifestation of ARC syndrome in Korean children is relatively mild and survival rate is higher than that of previous studies. Contrary to previous reports, this study showed that familial cases are rare and sporadic occurence is possible in Korea. Thus, the diagnosis of this syndrome requires a careful evaluation of the venal function in cases of congenital arthrogryposis, and a mandatory genetic counseling of affected family for prevention of familial occurance. (J Korean Soc Pediatr Nephrol 2005;9:222-230)

• Childhood Kidney Diseases
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• v.8 no.1
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• pp.18-25
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• 2004

Purpose : Alport syndrome is clinically characterized by hereditary progressive nephritis causing ESRD with irregular thickening of the GBM and sensory neural hearing loss. The mutations of type IV collagen gene(COL4A5) located on the long arm of X chromosome is considered responsible for most of the structural abnormalities in the GBM of Alport patients. Since no definite clinical prognostic predictor has been reported in the disease yet, we designed this study to evaluate the significance of genetic polymorphism of the angiotensin converting enzyme in children with Alport syndrome as a prognostic factor for disease progression. Methods : ACE I/D genotype were examined by PCR amplification of the genomic DNA in 12 patients with Alport syndrome and 12 of their family members. Alport patients were divided into two groups; the conservative group, those who had preserved renal function for more than 10 years of age, the early CRF group, those who had progressed to CRF within 10 years of age. Results : The mean age of onset was $3.45{\pm}2.4$ years in the conservative group, $4.4{\pm}1.2$ years in the early CRF group. Sex ratios were 5:3 and 2:1 in each group. Among 12 cases of patients, 4 cases were in early CRF group and their mean duration of onset to CRF was 4.5 yews(8.9 years of age). Eight patients(67%) were in the conservative group and they had normal renal function for more than 10 years of age(mean duration of renal preservation was 10.6 years). The incidence of II type ACE gene were in 25.0%(3 cases), ID type in 41.7%(5 cases), DD type in 33.3%(4 cases). There was no significant difference between Alport patient and normal control(II type 44.3%, ID type 40.9%, DD type 14.8%). The incidence of DD type of early CRF group were higher than that of the conservative group(75% vs 12.5%)(p<0.05). There was no difference in ACE gene polymorphism between normal Alport family members and control group. Conclusion : Even though there was no significant difference of ACE polymorphism between Alport patients and the normal control group, the incidence of DD type is significantly increased in early CRF group which means DD type of ACE polymorphism has a possibility of being a predictor for early progression to CRF in Alport patients.

• Journal of Preventive Medicine and Public Health
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• v.7 no.1
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• pp.1-28
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• 1974

The writers have conducted the investigation to assess the nutritional status of young rural Korean children aged from 0 to 4 years old in August 1971. The survey areas were Kaejong-myon. Daeya-myon, Okku-gun, Jeonra-bukdo, Korea. These survey areas were typical agricultural plain areas. The total numbers of children examined were 2,706 comprising 1,394 male and 1,312 female. The weight, height, and chest circumference of children were measured and means and standard deviations. were calculated for each measurement. In addition, the nutritional status of each child was classified by the four levels of malnutrition and the Gomez classification, The examination of red blood cell count, haematocrit value, and intestinal parasite infection were carried out at the same time. In general, recent work tend to suggest that environmental influences, especially nutrition, are of great importance than genetic background or other biological factors for physical growth and development. Certainly the physical dimensions of the body are much influenced by nutrition, particularly in the rapidly growing period of early childhood. Selected body measurements can therefore give valuable information concerning protein-calory malnutrition. Growth can also be affected by bacterial, viral, and parasitic infection. For the field workers in a developing country, therefore, nutritional anthropometry appears to be of greatest value in the assessment of growth failure and undernutrition, principally from lack of protein and calories. In order to compare and evaluate the data obtained, the optimal data of growth from the off-spring of the true well-fed, medically and socially protected are needed. So-called 'Standards' that have been compiled for preschool children in Korea, however, are based on measurement of children from middle or lower socio-economic groups, who are, in fact, usually undernourished from six months of age onwards and continuously exposed to a succession of infective and parasitic diseases. So that, the Harvard Standards which is one of the international reference standards was used as the reference standards in this study. Findings of the survey were as follows: A. Anthropometric data: 1) Comparing the mean values for body weight obtained with the Korean standard weight of the same age, the rural Korean children were slightly haevier than the Korean standard values in both sexes. Comparing with the Japanese children values, the rural Korean children were slightly haevier in male and in the infant period of female but lighter in female of the period of 1 to 4 years old than Japanese children. 2) Comparing the mean values for height obtained with the Korean standard height of the same age, the rural Korean children were taller than the Korean standard values except the second half of infatn period in both sexes. Comparing with the Japanese children, the rural Korean children were slightly smaller than Japanese children except the first half of infant peroid in both sexes. 3) Mear values of chest circumference of rural Korean children obtained were less than the Korean standard values of the same ages in both sexes. B. Prevalence of Protein-Calory Malnutrition: Children examined were devided into two groups, i. e., infant(up to the first birthday) and toddler (1 to 4 fears old). 1) Percentages of four levels of malnutrition: a) When the nutrtional status of each child was classified (1) by body weight value, the percentages for male and female of children attained standard growth were 52.8%(infant 83.3%, toddler 44.4%) and 39.7% (infant 74.5%. toddler 30.5%), the first level of malnutrition were 31.9%(infant 13.7%, toddler 36.9%) and 31.7%(infant 15.3%, toddler 36,0%), the second level of malnutrition were 12.3%(infant 1.7%, toddler 15.3%) and 23.3% (infant 7.7%, fodder 27.5%), the third level of malnutrition were 2.7%(infant 0.7%, toddler 3.2%) and 4.6%(infant 1.8%, toddler 5.3%) the fourth level of malnutrition were 0.3% (infant 0.7%, toddler 0.2%) and 0.7% (0.7% for infant and toddler) respectively. (2) by height value, the percentages for male and female of children attained standard growth were 80.3% (infant 97.3%, toddler 75.6%) and 75.1% (infant 96.4%, toddler 69.5), the first level of malnutrition were 17.9% (infant 2.0%, toddler 22.3%) and 23.6% (infants 3.6%, toddler 28.8%), the second level of malnutrition were 1.2% (infant 0.3%, toddler 1.5%) and 1.1% (infant 0%, toddler 1.4%), the third level of malnutrition were 0.4%(infant 0.3%, toddler 0.5%) and 0.2%(infant 0%, toddler 0.3%), the fourth level of malnutrition were 0.1%(infant 0%, toddler 0.1%) and 0% respectively. (3) by body weight in relation to height, the percentages for male and female of children attained standard growth were 87.9% (infant 77.6%, toddler 87.9%) and 78.2% (infant 77.4%, toddler 78.2%), the first level of malnutrition were 12.2% (infant 18.4%, toddler 10.6%) and 18.2% (infant 17.9%, toddler 18.3%), the second level of malnutrition were 1.9%(infant 3.3%, toddler 1.5%) and 3.0%(infant 3.3%, toddler 2.9%), the third level of malnutrition were 0.1%(infant 0%. toddler 0.1%) and 0.5% (infant 0%, toddler 0.6%), the fourth level of malnutrition were 0.1%(infant 0.7%, toddler 0%) and 0.3% (infant 1.5%, toddler 0%) respectively. b) When the nutritional status of each child according to the mother's age at perturition, i. e., young aged mother (up to 30 years old), middle aged mother (31 to 40 years old) and old aged mother (41 years or above) was classified (1) by body weight, among infants and toddlers, at each year of age, with increasing the mother's age, there was an increase in percentage of subjects underweight. This tendency of increasing percentage of underweight was more significant in the infant period than the toddler period. (2) by height value, no significant differences between each mother's age group were found. c) When the nutritional status of each child according to the birth rank, i. e., lower birth rank (first to third) and higher birth rank (fourth or above) was classified (1) by weight value, children of higher birth rank were slightly more often underweight than those of lower birth rank, but not significant. (2) by height value, no differences were found between children of lower and higher birth rank. 2) Gomez Classification: When the nutritional status of each child was classified a) by body weight value, the percentages for male and female of children. attained standard growth were 53.1% (infant 82.6%, toddler 44.9%) and 39.2% (infant 73.4%, toddler 30.1%), the first degree of malnutrition were 39.4% (infant 14.7%, toddler 46.2%) and 47.1% (infant 21.9%, toddler 53.8%), the second degree of malnutrition were 7.3%(infant 2.3%, toddler 8.6%) and 12.9% (infant 4.0%, toddler 15.2%). and the third degree of malnutrition were 0.2%. (infant 0.3%, toddler 0.2%) and 0.8% (infant 0.7%, toddler 0.9%) respectively. b) by height value, the percentages for male and female of children attained standard growth were 80.8% (infant 97.0%, toddler 76.3%) and 73.8%(infant 95.6%, toddler 68.0%), the first degree of malnutrition were 18.5% (infant 2.7%, toddler 22.9%) and 24.6% (infant 4.4%, toddler 30.0%), the second degree of malnutrition were 0.6%(infant 0.3%, toddler 0.7%) and 0.5% (infant 0.1%, toddler 0.7%), and the third degree of malnutrition were 0.1%(infant 0%, toddler 0.1%) and 1.1% (infant 0%, toddler 1.3%) respectively. C. Results of clinical laboratory examination: 1) Red blood cells: The ranges of mean red blood cell counts for male and female were $3,538,000/mm^3\;to\;4,403,000/mm^3\;and\;3,576,000/mm^3\;to\;4,483,000/mm^3$ respectively. The lowest red cell counts were seen at the age of 0-3 months for male and 1-2 months for female. 2) Haematocrit value : The ranges of haematocrit value of male and female were 35.1% to 38.8% and 34.7% to 38.8% respectively. The lowest haematocrit values were seen at the age of 2-3 months for male and 1-2, months for female. 3) The prevalence rates of intestinal parasites for male and female children with Ascaris lumbricoides were 34.1% (infant 18.8%, toddler 38.1%) and 36.0%(infant 18.4%, toddler 40.7%), with Trichocephalus trichiuris were 6.8% (infant 2.9%, toddler 7.9%) and 9.0% (infant 3.0%, toddler 10.6%), with Hookworm were 0.3% (infant 0.5%, toddler 0.2%) and 0.3% (infant 0.5%, toddler 0.3%), with Clonorchis sinensis were 0.4%(infant 0%, toddler 0.5%) and 0.1%(infant 0%, toddler 0.1%) respectively.