Genetic Variations of Eight Candidate Genes in Korean Obese Group

Kang, Byung-Youn,Lee, Kang-Oh,Bae, Joon-Seol,Kim, Ki-Tae,Yoon, Moon-Young,Lim, Seok-Rhin,Seo, Sang-Beom,Shin, Jung-Hee,Lee, Chung-Choo Korean Environmental Mutagen Society 2002 한국환경성돌연변이·발암원학회지 Vol.22 No.1

Obesity is a complex metabolic disorder with a strong genetic component. There are many candidate genes for obesity and its related phenotypes. We studied genetic variations between Korean obese and lean groups. Polymorphisms investigated were the Msp I polymorphism of the $\alpha$$_{2A}$-adrenergic receptor ($\alpha$$_{2A}$-AR) gene, the Mnl I polymorphism of the $\alpha$$_2$-adrenergic receptor ($\alpha$$_2$-AR) gene, the BstO I polymorphism of the $\beta$$_3$-adrenergic receptor ($\beta$$_3$-AR) gene, the Pml I polymorphism of the lamin A/C (LMNA) gene, the Hga I polymorphism of the clearance receptor (NPRC) gene, the Msp I polymorphism of the leptin gene, BclI polymorphism of the uncoupling protein 1 (UCPI) gene and the Hha I polymorphism of the fatty acid binding protein 2 (FABP2) gene. Among these genetic markers, Pml I polymorphism at the LMNA gene and Bcl I polymorphism at the UCP1 gene were significantly associated with obesity. However, further studies are required whether thease findings are reproduced in large population, although two polymorphisms might be useful as genetic markers in the ethiology of obesity in Korean population.ion.

Relationship between angiotensin-converting enzyme gene polymorphism and muscle damage parameters after eccentric exercise

( Joo Young Kim ),( Chang Sun Kim ),( Joo Hyung Lee ) 한국운동영양학회 2013 Physical Activity and Nutrition (Phys Act Nutr) Vol.17 No.2

This study was conducted to investigate the relationship between ACE gene polymorphism and muscle damage parameters after eccentric exercise. 80 collegiate males were instructed to take an eccentric exercise with the elbow flexor muscle through the modified preacher curl machine for 2 sets of 25 cycles (total 50 cycles). The maximal isometric strength, muscle soreness, creatine kinase (CK), and myoglobin (Mb) were measured before exercise, and 0, 24, 48, 72, and 96 hrs after exercise. The result showed that after the eccentric exercise, the maximal isometric strength significantly decreased by more than 50% (p < 0.001) and the muscle soreness, CK, and Mb significantly increased compared to those before the exercise (p < 0.001). The ACE gene polymorphism of the subjects was classified using real-time polymerase chain reaction (real-time PCR). The result showed that it consisted of 38 cases of type II (46.4%), 33 cases of type ID (43.4%), and 9 cases of type DD (10.2%). The Hardy-Weinberg equilibrium for ACE gene polymorphism was shown to have p = 0.653, which showed that each allele was evenly distributed. Although significant differences in the changes in the maximal isometric strength, muscle soreness, CK, and Mb were found according to time course (p < 0.001), no significant differences in the changes in the maximal isometric strength, muscle soreness, CK, and Mb were found according to ACE gene polymorphism. Furthermore, no significant difference in the changes in the muscle damage parameters was found according to interaction between ACE gene polymorphism and time course (p > 0.05). In conclusion, the level of the muscle damage parameters changed in the injured muscle after eccentric exercise, but these changes in the muscle damage parameters were not affected by ACE gene polymorphism. The result of this study indicates that ACE gene is not a candidate gene that explains muscle damage.

Polymorphism of Estrogen Receptor Genes and Its Interactions With Neurodevelopmental Genes in Attention Deficit Hyperactivity Disorder Among Chinese Han Descent

Yiwei Lin,Haimei Li,Jing Zhang,Ziqi Yang,Yi Zhou,Lu Liu,Qiujin Qian 대한신경정신의학회 2023 PSYCHIATRY INVESTIGATION Vol.20 No.8

Objective Attention deficit hyperactivity disorder (ADHD) is a polygenic neurodevelopmental disorder with significant gender differences. The sexual dimorphism of ADHD may be associated with estrogen acting through estrogen receptors (ESR). This study investigates the impact of <i>ESR</i> gene polymorphism and its interactions with neurodevelopmental genes on ADHD susceptibility.Methods The study compared genotyping data of single nucleotide polymorphisms in <i>ESR1</i> and <i>ESR2</i> in 1,035 ADHD cases and 962 controls. The gene-gene interactions between <i>ESR</i> genes and three neurodevelopmental genes (brain-derived neurotrophic factor [<i>BDNF</i>], synaptosomal-associated protein of 25 kDa gene [<i>SNAP25</i>], and cadherin-13 [<i>CDH13<i></i></i>]) in ADHD were investigated using generalized multifactor dimensionality reduction and verified by logistic regression analysis.Results The G allele of rs960070/<i>ESR2</i> (empirical p=0.0076) and the A allele of rs8017441/<i>ESR2</i> (empirical p=0.0426) were found significantly higher in ADHD cases than in the controls but not in male or female subgroups. Though no difference was found in all subjects or females, the A allele of rs9340817/<i>ESR1</i> (empirical p=0.0344) was found significantly higher in ADHD cases than controls in males. We also found genetic interaction models between <i>ESR2</i> gene, neurodevelopmental genes and ADHD susceptibility in males (<i>ESR2</i> rs960070/<i>BDNF</i> rs6265/<i>BDNF</i> rs2049046/<i>SNAP25</i> rs362987/<i>CDH13</i> rs6565113) and females (<i>ESR2<i></i></i> rs960070/<i>BDNF<i></i></i> rs6265/<i>BDNF</i> rs2049046) separately, though it was negative in overall subjects.Conclusion The <i>ESR</i> gene polymorphism associates with ADHD among Chinese Han children, with interactions between <i>ESR<i></i></i> genes and neurodevelopmental genes potentially influencing the susceptibility of ADHD.

Genetic Variations in Six Candidate Genes for Insulin Resistance in Korean Essential Hypertensives

Bae, Joon-Seol,Kang, Byung-Yong,Kim, Ki-Tae,Shin, Jung-Hee,Lee, Chung-Choo The Korean Society for Integrative Biology 2001 Korean journal of biological sciences Vol.5 No.4

Hypertension is a complex disease with strong genetic influences. Essential hypertension has been shown to be associated with insulin resistance. To clarify the genetic basis of insulin resistance in Hypertension, case-control association studies were performed to examine candidate genes for insulin resistance in hypertension. Polymorphisms investigated were the BstO I polymorphism of the $\beta$3-adrenergic receptor (ADRB3) gene, the Xba I Polymorphism of the glycogen synthase (GSY) gene, the Dde I polymorphism of the protein phosphatase 1 G subuit (PP1G) gene, the BstE II polymorphism of the glucagon receptor (GCG-R) gene, the Pst 1 polymorphism of the insulin (INS) gene and the Acc I polymorphism of the glucokinase (GCK) gene. No significant differences were observed in the distribution of alleles and genotypes of the ADRB3, GSY PP1G, GCG-R, INS, and GCK genes between hypertensive and normotensive groups. Although the frequencies in each of these polymorphisms were not significantly different between essential hypertensive and normotensive individuals, our results may provide additional information for linkage analysis and associative studies of disorders in carbohydrate metabolism or in cardiovascular disease.

Identification and Characterization of Human Genes Targeted by Natural Selection

Ryu, Ha-Jung,Kim, Young-Joo,Park, Young-Kyu,Kim, Jae-Jung,Park, Mi-Young,Seo, Eul-Ju,Yoo, Han-Wook,Park, In-Sook,Oh, Berm-Seok,Lee, Jong-Keuk Korea Genome Organization 2008 Genomics & informatics Vol.6 No.4

The human genome has evolved as a consequence of evolutionary forces, such as natural selection. In this study, we investigated natural selection on the human genes by comparing the numbers of nonsynonymous (NS) and synonymous (S) mutations in individual genes. We initially collected all coding SNP data of all human genes from the public dbSNP. Among the human genes, we selected 3 different selection groups of genes: positively selected genes (NS/S${\geq}$3), negatively selected genes (NS/S${\leq}$1/3) and neutral selection genes (0.9<NS/S<1.1). We characterized human genes targeted by natural selection. Negatively selected human genes were markedly associated with disease occurrence, but not positively selected genes. Interestingly, positively selected genes displayed an increase in potentially deleterious nonsynonymous SNPs with an increased frequency of tryptophan and tyrosine residues, suggesting a correlation with protective effects against human disease. Furthermore, our nonsynonymous/synonymous ratio data imply that specific human genes, such as ALMS1 and SPTBN5 genes, are differentially selected among distinct populations. We confirmed that inferences of natural selection using the NS/S ratio can be used extensively to identify functional genes selected during the evolutionary adaptation process.

성장기 아동의 IGF-I 유전자 다형성에 따른 혈중 IGF-I 분비양상과 신체구성, 골 연령 및 12주 복합 운동의 효과

김기진 ( Ki Jin Kim ) 대한스포츠의학회 2012 대한스포츠의학회지 Vol.30 No.1

Association of insulin like growth factor (IGF)-I gene polymorphism with blood concentration of IGF-I, body composition, bone age and response to combined exercise program in teen-aged children. The purpose of this study was to determine whether there are the differences of blood concentration of IGF-I, body composition, bone age and response to combined exercise program according to IGF-I gene polymorphism in Korean teen-aged children. Subjects were recruited by 143 teen-aged children (male: 78, female: 65) from elementary school. Twelve weeks exercise program was consisted of resistance training and aerobic exercise. For the comparison of items and responses to combined exercise program according to IGF-I gene polymorphism, blood concentration of IGF-I, skinfold thickness, body circumferences, and growth markers were measured at baseline and after intervention. Body weight, %fat, BMI, skinfold thickness, circumferences, blood concentration of IGF-I, and bone age showed no significant differences following to IGF-I gene polymorphism. Although body composition and blood concentration of IGF-I showed a positive change after 12 week exercise training, 12 week exercise-mediated changes of body composition and blood concentration of IGF-I showed no significant differences following to IGF-I gene polymorphism. In conclusion, IGF-I gene polymorphism no contributed to the differences of body composition, blood concentration of IGF-I, and 12 week exercise-mediated these changes in teen-aged children.

한국 소아 1형 당뇨병에서 종양괴사인자 및 림프독소-α 유전자 다형성

서진순,박소영,정민호,서병규,김태규,이병철,Suh, Jin Soon,Park, So Young,Jung, Min Ho,Suh, Byung Kyu,Kim, Tae Gyu,Lee, Byung Churl 대한소아청소년과학회 2005 Clinical and Experimental Pediatrics (CEP) Vol.48 No.8

목 적 : 한국 소아 1형 당뇨병에서 TNF promoter -857T/C와 -1031C/T 및 $LT-{\alpha}$ 유전자 다형성과 질병감수성과의 관련성을 평가하고자 하였다. 방 법 : 1형 당뇨병으로 진단 받은 소아 49명(여아 29명, 남아 20명)과 정상 대조군 94명의 혈액을 채취하여 DNA를 추출하였다. 추출한 DNA에 대하여 allele-specific PCR법을 이용하여 TNF promotor -1031C/T 다형성을, PCR-RFLP법을 이용하여 TNF promotor -857T/C, $LT-{\alpha}$ 유전자 다형성을 분석하였다. 결 과 : 환자군과 대조군 사이에서 TNF promoter -857T/C, -1031C/T 다형성의 분포는 차이가 없었다. 환자들의 임상적 특징에 따라 아군(subgroup)으로 분류하였을 때, 진단 시 당뇨병성 케톤산혈증으로 발현한 환자들에서 TNF promoter -1031C/T 다형성의 TT 유전자형의 빈도가 당뇨병성 케톤산혈증으로 발현하지 않은 환자들과 비교하여 유의하게 낮았다(P<0.05). 다른 임상적 특성들과 이들 유전자 다형성 사이에는 관련성이 없었다. 또 환자와 대조군 사이에 $LT-{\alpha}$ 유전자 다형성의 분포는 차이가 없었으며, 임상적 특성과의 관련성도 없었다. 결 론 : 이 연구를 통하여 TNF promoter -857T/C, $LT-{\alpha}$ 유전자 다형성이 한국 소아에서 1형 당뇨병의 질병감수성과 관련이 없음을 알 수 있었다. 그러나 TNF promoter -1031C/T 다형성은 당뇨병성 케톤산혈증과 같은 1형 당뇨병의 특정 임상양상에 영향을 미칠 수 있는 유전적 인자로 생각된다. Purpose : Recently, it was reported that tumor necrosis factor(TNF) and $lymphotoxin-{\alpha}$($LT-{\alpha}$) gene regions might be a susceptible loci to type 1 diabetes in Japanese. The purpose of this study was to investigate the association of TNF and $LT-{\alpha}$ gene polymorphisms with disease susceptibility in Korean children with type 1 diabetes. Methods : Forty-nine Korean children with type 1 diabetes(29 girls and 20 boys) and 94 healthy Koreans were investigated in this study. Genotyping for -857T/C polymorphism in the TNF promoter region and $LT-{\alpha}$ gene polymorphism were performed by PCR-RFLP(restriction fragment length polymorphism). TNF promoter -1031C/T polymorphism was detected by allele-specific PCR. Results : The distribution of the -857T/C and -1031C/T genotype in the TNF promoter region was not different between diabetic children and the controls. The frequency of TT genotype in the distribution of TNF -1031C/T polymorphism in diabetic children with diabetic ketoacidosis(DKA) at diagnosis was significantly lower than those without DKA(P<0.05). No significant difference in the distribution of $LT-{\alpha}$ gene polymorphism was observed between diabetic children and the controls. There was no association between clinical characteristics of type 1 diabetes and $LT-{\alpha}$ gene polymorphisms. Conclusion : These results suggest that TNF promoter -857T/C and $LT-{\alpha}$ gene polymorphisms are not associated with susceptibility to type 1 diabetes in Korean children. TNF promoter -1031C/T polymorphism might be related to clinical manifestations(DKA) of type 1 diabetes.

Relationship between angiotensin-converting enzyme gene polymorphism and muscle damage parameters after eccentric exercise

김주영,김창선,이주형 한국운동영양학회 2013 Physical Activity and Nutrition (Phys Act Nutr) Vol.17 No.2

This study was conducted to investigate the relationship between ACE gene polymorphism and muscle damage parameters after eccentric exercise. 80 collegiate males were instructed to take an eccentric exercise with the elbow flexor muscle through the modified preacher curl machine for 2 sets of 25 cycles (total 50 cycles). The maximal isometric strength, muscle soreness, creatine kinase (CK), and myoglobin (Mb) were measured before exercise, and 0, 24, 48, 72, and 96 hrs after exercise. The result showed that after the eccentric exercise, the maximal isometric strength significantly decreased by more than 50% (p < 0.001) and the muscle soreness, CK, and Mb significantly increased compared to those before the exercise (p < 0.001). The ACE gene polymorphism of the subjects was classified using real-time polymerase chain reaction (real-time PCR). The result showed that it consisted of 38 cases of type II (46.4%), 33 cases of type ID (43.4%), and 9 cases of type DD (10.2%). The Hardy-Weinberg equilibrium for ACE gene polymorphism was shown to have p = 0.653, which showed that each allele was evenly distributed. Although significant differences in the changes in the maximal isometric strength, muscle soreness, CK,and Mb were found according to time course (p < 0.001), no significant differences in the changes in the maximal isometric strength,muscle soreness, CK, and Mb were found according to ACE gene polymorphism. Furthermore, no significant difference in the changes in the muscle damage parameters was found according to interaction between ACE gene polymorphism and time course (p > 0.05). In conclusion, the level of the muscle damage parameters changed in the injured muscle after eccentric exercise, but these changes in the muscle damage parameters were not affected by ACE gene polymorphism. The result of this study indicates that ACE gene is not a candidate gene that explains muscle damage.

베타3-아드레날린 수용체 유전자 다형성에 따른 지적장애인의 체력 및 인슐린저항성 비교

이민희,윤진호,오재근 한국운동재활학회 2011 JER Vol.7 No.3

The purpose of this study was to examine the relationship between physical fitness of people with mental retardation and insulin resistance according to β3-AR gene polymorphism. 13-17 aged people with mental retardation were selected and all subjects can communicate, have been not take antipsychotic drugs. The investigator confirmed the polymorphism of β3-AR gene via PCR technique and divided subjects into two groups(Trp/Trp, Trp/Arg). Through this study the distributions of β3-AR gene polymorphism and difference in the Physical fitness factors(6m PACER, modified curl-ups, trunk flection), body composition(height, body weight, BMI, waist measurement, hip circumference, diastolic BP, systolic BP, heart rate) and blood factosr(total cholesterol, high-density lipoprotein cholesterol, triglyceride, glucose, insulin resistance and insulin) were identified. To examine the difference between two groups according to the β3-AR gene polymorphism, independent sample t-test was carried out using SPSS/PC16.0. Study findings are as follows: There is no significant difference in such obesity factors as body fat and WHR, systolic blood pressure, diastolic blood pressure and stabilized heart rate according to the obese gene polymorphism. The 16m PACER and modified curl-ups were higher in the TT group and it was statistically significant. The trunk flexion forward, which presenting flexibility, was higher in the TT group than the TA group, but it was not statistically significant. Blood glucose and insuline resistance were higher in the TA group significantly. There was no significant difference in total cholesterol, TG, HDL and insulin. Although the β3-AR obese gene polymorphism cannot be directly regarded as the cause of obesity, its relationship with physical fitness and insuline resistance was confirmed in this study. Therefore, if the β3-AR gene polymorphism is checked in advance, obesity and secondary cardiovascular disease could be prevented. In addition, the confirmation of β3-AR obese gene polymorphism in advance seemingly has a positive effect as basic data for the working out of a health maintenance and promotion program.

정신분열병 환자에서 도파민 D₃ 및 세로토닌 5-HT2a 수용체 유전자의 유전적 다형성 분석

김윤원(Yoon Won Kim),한진영(Jin-Yeong Han),김성환(Seong Hwan Kim),한홍무(Hong Moo Hahn),최병무(Byeong Moo Choe) 대한생물치료정신의학회 2002 생물치료정신의학 Vol.8 No.2

연구목적 : 도파민 D₃ 수용체 유전자(DRD₃)와 세로토닌 5-HT2a 수용체 유전자(5-HT2aR)의 유전적 다형성 분석을 하여 정신분열병과 이들 유전자와의 상관성 여부를 확인하고자 유전학적 연구를 시행하였다. 방법 : 각각 100명의 정신분열병 환자 및 정상 대조군을 대상으로 말초혈로부터 genomic DNA를 분리하여 DRD₃와 5-HT2aR 유전자에 각각 특이 primer를 사용하여 중합효소연쇄반응(polymerase chain reaction : PCR)을 실시하였다. 증폭한 유전자를 각기 제한효소 절편분석반응을 시행하여 유전자의 유전적 다형성 분석을 시행하였으며 이렇게 분류된 유전자형을 환자군과 정상 대조군에서 상호 비교하기 위하여 통계 분석하였다. 결과 : 증폭한 DRD₃ 유전자를 MscI 제한효소로 절단하여 절편분석을 하였을 때 304bp의 band를 보인 군(-/-), 304bp, 206bp 및 98bp의 세 개의 band를 보인 군(+/-), 그리고 206bp와 98bp의 두 개 band를 보인 군(+/+)이 각각 정신분열병 환자군에서 47명,45명, 8명이었고 정상 대조군에서는 61명, 34명, 5명으로서 두 군 간에 통계적으로 유의한 차이는 없었다(p=0.l32). 5-HT2aR 유전자의 MspI 제한효소 다형성 분석에서도 372bp(-/-), 372bp, 216bp와 156bp(+/-), 그리고 216bp와 156bp(+/+)를 보이는 경우가 정신분열병 환자군과 정상 대조군에서 각각 33명, 48명, 19명과 35명, 48명 17명으로 두 군 사이에 통계적 유의성을 보이지 않았다(p=0.918). 결론 : 본 연구결과는 한국인에 있어서 DRD₃ 유전자와 5-HT2aR 유전자는 정신분열병의 원인이 아닐 가능성을 제시한다. Background : Previous family, twin and adoption studies suggested that genetic factors playa major role in the etiology of schizophrenia. However, the mode of inheritance, like that of other common disorders, is complex and it is generally believed that more than one gene is involved in the genetics of schizophrenia. In the present study, the authors examined 100 unrelated Korean schizophrenics and 100 Korean normal controls, all belonging to a single ethnic population, to determine any association between genetic polymorphisms in the dopamine D₃ receptor(DRD₃) gene and the 5-hydroxytryptamine type 2a receptor(5-HT2aR) gene and schizophrenia. Methods : High molecular weight genomic DNA was extracted from whole blood of 100 schizophrenics and 100age- and sex-matched healthy controls. The Mscl polymorphism of DRD₃ gene and the Mspl of 5-HT2aR gene were typed by restriction enzyme digestion after amplification of genomic DNA by polymerase chain reaction. Genotypic distributions were analyzed using the χ² test. Results : With regard to Mscl/DRD₃ gene polymorphism, the presence of 304bp band denoted a (-/-) homozygote, 3 bands at 304bp, 206bp, and 98bp, a (+/-) heterozygote, and 2 bands at 206bp and 98bp, a (+/+) homozygote. In Mspl/5-HT2aR gene polymorphism, a (-/-) homozygote with a 372bp, a (+/-) heterozygote with 3 bands of 372bp, 216bp, and 156bp, a (+/+) homozygote with 2 bands of 216bp and 156bp were identified. No significant positive association between either the DRD₃ genotype or the 5-HT2aR genotype and schizophrenia was observed. Conclusion : Significant association was not observed between schizophrenia and any of the two polymorphisms at the DRD₃ gene and the 5-HT2aR gene. The results suggest that the DRD₃ and 5-HT2aR polymorphisms may not be involved in the genetic susceptibility to the Korean schizophrenics.