Association between glutathione S-transferases M1, T1 and P1 gene polymorphisms and prostate cancer in Koreans

진한준,신예은,황인욱 한국유전학회 2016 Genes & Genomics Vol.38 No.2

Prostate cancer (PCa) is the most commonly diagnosed cancer in the developed world, and the incidence of this cancer is rising rapidly in many countries. Several polymorphic genes encoding enzymes involved carcinogenesis have been studied as potential risk factor of prostate cancer. Genetic polymorphisms in glutathione S-transferases M1 (GSTM1), T1 (GSTT1) and P1 (GSTP1) genes have been constantly reported to have a meaningful effect on prostate cancer risk. But other surveys of this relationship have yielded inconsistent results. To assess the possible contribution of the GSTM1, GSTT1, and GSTP1 gene polymorphisms in prostate cancer, we performed a population-based study of 139 prostate cancer patients and 115 healthy controls based on their genotype distributions of the genes. There were no differences in distributions of genotype frequencies of GSTM1 and GSTP1 polymorphisms between prostate cancer patients and controls (OR 1.60, 95 % CI 0.886–2.860 for GSTM1 and OR 1.38, 95 % CI 0.739–2.577 for GSTP1). In contrast, the distribution of GSTT1-null genotype is significantly different between the prostate cancer case and controls (OR 0.26, 95 % CI 0.128–0.518, p\0.001). Meanwhile, GSTP1 I/V and V/V genotypes were significantly associated with prostate cancer where the PSA level was more than 10.0 (OR 2.73, 95 % CI 1.319–5.639, p = 0.006). Thus, our data imply that the GSTT1-null genotype may not be a risk factor but a protective factor of prostate cancer and GSTP1 Val allele is a risk factor for the prostate cancer where the PSA level was high, although functional studies with larger sample size are necessary to elucidate these findings.

Y-chromosome Haplogroup C Lineages and Implications for Population History of Korea

진한준,곽경돈,홍승범,김욱 한국유전학회 2006 Genes & Genomics Vol.28 No.3

We analyzed Y-chromosome variation for identification of haplogroup C lineages (RPS4Y711transition) in 680 males from eleven ethnic groups in east Asia to study the male lineage history of Korea. The haplogroup C lineages were further typed with the M217 binary marker to define the lineage C3, together with six Y-STR markers for evaluation of population diversity. Our result is consistent with previous reports that the lineages C3 were common in northeast Asia (especially, Mongolia), while these M217-derived lineages were absent in haplogroup C lineages seen in most southeast Asia, except for the Yunnan-Han and Vietnamese populations. The moderate frequency of haplogroup C3 lineages(14.9%) and their high genetic diversity of Y-STR haplotypes (>0.99) in Korea imply population diversification and deep population depth, as well as a genetic influence from northern populations of east Asia. The occurrence of high frequencies of the M217 sublineages and their low genetic diversities in Siberia might be not only a result of the influence of genetic drift and founder effect, but also diversification resulting from the prehistoric northward migration of the haplogroup C lineages.

Phylogenetic analysis of two haploid markers of 500-years-old human remains found in a central region of Korea

진한준,김기철,김욱 한국유전학회 2015 Genes & Genomics Vol.37 No.1

To understand the genetic history of maternal/paternal lineages of Koreans, we analyzed two haploidmarkers, mitochondrial DNA (mtDNA), and Y-chromosomalvariations, in 25 human remains (dated at about400–600 years old) excavated from a central region ofKorea (Yangchon cemetery of Gimpo-si, Gyeonggi-do). MtDNA control region (HVS-I/II) sequences of 19 ancienthuman samples from a total of 25 remains were successfullydetermined by sequencing after PCR-cloning anddirect sequencing techniques. Among the 25 remains, 12individuals were found to be males determined by theamelogenin locus using PCR amplification. We found thatthe vicinal burial of the remains seemed to be relatedmatrilineally or patrilineally. The most common mtDNAhaplogroups were found to be D4a (5/19), followed by D4(3/19), F1bde (3/19), D4c (2/19), D4g2a (1/19), B5b (1/19),F (1/19), F1a1 (1/19), G4 (1/19), and N9a (1/19), which areprevalent in the Northeast and Southeast Asians, includingmodern Koreans. On the paternal side, there are threedominant Y chromosome haplogroups C (41.7 %), O3(25 %), and Y* (33.3 %) in total male samples. The phylogeneticanalysis of the mtDNA HVS-I sequence variationrevealed both the overall similarity to other northeasternpopulations, and also a larger genetic contribution fromsoutheastern populations. Thus, these results are consistentwith previous reports that the peopling of Korea is likely tohave involved multiple sources. Larger sample sizes andadditional genetic markers will be necessary to fullyunderstand the population structure and the genetic historyof the Koreans.

Forensic Genetic Analysis for the PowerPlex-16 System in the Korean Population

진한준,곽경돈,홍승범,조율희,한면수,김욱 한국유전학회 2007 Genes & Genomics Vol.29 No.4

We have analyzed 15 short tandem repeat (STR) markers included the Power Plex-16 (Promega) kit in a sample of 165 unrelated individuals from Korforensic parameters were calculated to provide an expanded and reliable forensic database. The Exact Test demonstrated that al loci surveyed here were found to be no deviation from Hardy-Weinberg equilibrium. Statistical analyses based on allele frequencies of the 15 STR loci show that twelve Eurasian populations tested can be clasified into two distinct clusters; apanese of the East Asian cluster but tend to be diferent from the European cluster. The calculated parameters showed Penta E to be the most valuable marker from the STR loci studied. The combined probability of match calculated from 15 STR loci was 2.19× 10-17, which is highly informative. Our data, r STRs, as wel as provide valuable information for forensic and population genetic studies in the Korean population.

Y-chromosome Haplogroup O3-M122 Variation in East Asia and Its Implications for the Peopling of Korea

홍승범,진한준,곽경돈,김욱 한국유전학회 2006 Genes & Genomics Vol.28 No.1

The analysis of Y-chromosome variation has become a useful tool for studies of the prehistoric migration route(s) and population expansions in human populations. A total of twelve Y-chromosome binary markers (D-YAP, C-RPS4Y711, M9, M214, M175, M119, P31, M95, SRY+465, DXYS5Y, M122, and LINE1) in 709 males from 11 ethnic groups was used to examine the distribution of the east Asian paternal lineages, and to evaluate the relative contribution of haplogroup O3-M122 lineages for the peopling of Korea. Our result is consistent with previous reports that the major Y-chromosomal expansions in east Asia were those of haplogroup O-M175 and its sublineages. Especially, haplogroup O3-M122 (a sublineage of haplogroup O-M175) appeared to be widespread and common in China and its surrounding regions. These results suggest that the haplogroup O3-M122 lineage may have originated mainland east Asia (probably southern China) and been extended into the surrounding populations. Thus, the earliest evidence of the ancient origins of east Asian agriculture and population studies imply that the preponderance of O3-M122, O2-P31, and their sublineages in Korea might be due to the influence of demographic process related to the early massive spreads of mainly male-mediated agriculture into the region.

Is there a relationship between PPARD T294C/PPARGC1A Gly482Ser variations and physical endurance performance in the Korean population?

김욱,진한준,황인욱,김기철,조현익,박태환,신윤아,이호성,황지현,김아람,이광희,신예은,이지연,김지애,최은지,김보경,심희섭,김민석 한국유전학회 2016 Genes & Genomics Vol.38 No.4

The peroxisome proliferator-activated receptor d (PPARD) and peroxisome proliferator-activated receptor c coactivator 1a (PPARGC1A) genes recently have been suggested to have an association with athletic performance and physical endurance. These gene products are reported to be crucial components in training-induced muscle adaptation, since they are related with mRNA and/or protein activity in coordinated response to exercise. To assess the possible contribution of the PPARD T294C/ PPARGC1A Gly482Ser polymorphism to differences in physical endurance, we performed a population-based study of 111 Korean athletes and 145 healthy controls based on their genotype distribution of the genes. The two loci were found to be not deviated from Hardy–Weinberg equilibrium. There were no differences in genotype distribution of PPARD T294C and PPARGC1A Gly482Ser between the athletic group and controls (p[0.05). In contrast, we found a significant association between the PPARGC1A Gly482Ser polymorphism and the 20 m shuttle run activity (a measure of endurance performance) in the athletic group (p = 0.003). The result showed a remarkable increase in the numbers of shuttle run ratio from subjects with the PPARGC1A Gly/Gly genotype (85.29 ± 28.80) than those with the Gly/Ser (58.05 ± 32.76) and Ser/Ser (68.38 ± 30.47) genotypes. Thus, our data imply that the PPARGC1A Gly/Gly genotype may provide a beneficial effect on elite-level endurance status, although functional studies with larger sample sizes are necessary to elucidate these findings.

Dissecting the genetic structure of Korean population using genome-wide SNP arrays

김영진,진한준 한국유전학회 2013 Genes & Genomics Vol.35 No.3

Genome-wide SNP arrays have generated unprecedented quantities of data allow the detection of human evolutionary history and dense genome-wide data also enable the identification of distance ancestry among individuals or ethnic groups. To explain wider aspects of the genetic structure of Koreans and the East Asian population,we analyzed 79 individuals from the Korean HapMap project at 555,352 common single-nucleotide polymorphism loci, and compared this data with the worldwide population groups with the 53 ethnic groups from Human Genome Diversity Panel (HGDP-CEPH). Population differentiation (FST), Principal Component Analyses, STRUCTURE and ADMIXTURE are examined. In general, all the individual samples studies here were classified into subset of ethnic groups according to their geographical origins. Korean HapMap individuals were grouped together with East Asian populations from HGDP panel. Recently, a sub-population structure within Korean population has been reported. Our result, however,revealed the genetic homogeneity of Korean population. The ADMIXTURE analysis showed that, overall the Korean populations derive 79 % of their genomic ancestry from southern Asia and have relatively little northern Asian ancestry (21 %). The present work, therefore, provide the evidence that the male-biased southern-to-northern migration influenced not only for the genetic make up of the Y chromosome in the Korean population but also, its autosomal composition.

Assessment of association of ACTN3 genetic polymorphism with Korean elite athletic performance

홍성수,진한준 한국유전학회 2013 Genes & Genomics Vol.35 No.5

Genetic and environmental factors have longbeen suspected to influence on physical performance andathletic ability. Recent studies have suggested that theskeletal-muscle actin binding protein a-actinin-3 (ACTN3)gene was associated with athletic performance in Europeans. It would lead us to hypothesize that ACTN3 gene maybe one of the factors that influence certain variation inmuscle function, but origins and replicate tests remain to beelucidated. We analyzed ACTN3 genetic polymorphism toassess the possible role of the genotype differences (RR, RX,and XX) in elite athletic performance in a population-basedcase-control study in Korea. The ACTN3 gene locus wasfound to be no deviation from Hardy–Weinberg expectation. We observed a significant association between femalesprint/power athletes (SPAs) and control (P = 0.028), thatof male SPAs or all SPA samples did not. The female SPAsappeared to have a dearth of 577 XX genotype (OR 0.104,95 % CI 0.013–0.822, P = 0.011) compared with thecontrol with a replicating finding in the Korean population. Thus, our results imply that the sex specific ACTN3 R577Xgenotype may provide a significant effect on elite Koreanfemale SPAs status, although larger sample sizes andfunctional studies are necessary to further elucidate thesefindings.

한국인 집단에서 미토콘드리아 DNA의 'Asian-specific 9-bp결실'다형현상

김욱,진한준 단국대학교 1999 論文集 Vol.34 No.-

Length changes in mitochondrial DNA (mtDNA) offer a useful marker for the study of female aspects of human population history. One such length change is the intergenic COⅡ/tRNA^Lys 9-bp deletion, which the region usually contains two tandemly arranged copies of a 9-bp sequence (ccccctcta) in human mtDNA. This deletion has been reported at varying frequencies in populations from Asia. Polynesia, the New World, and sub-Saharan Africa. This genetic polymorphism of mtDNA was analyzed in samples from 171 unrelated individuals from the Korean population and compared the frequency and distribution of 9-bp deletion with other Asian population. The frequency of the 9-bp deletion was found to be 17.5% (30/171) in the Korean populations. Uncommonly, a new insertion allele of approximately 6-bp in the intergenic COⅡ/tRNA^Lys region in the Korean population (2/171) was first identified in this study. East Asian populations including Chinese. Japanese, and Koreans were relatively homogeneous in the frequency of 9-bp deletion. with the exception of the low frequency of this deletion in Mongolians. On the other hand, Indonesians and Malaysians of Southeast Asian populations were found to show relatively high frequencies of the 9-bp deletion. Based on results of the frequencies of the 9-bp deletion, the Japanese population appeared to have a closer genetic relationship to Koreans than to the other surveyed Asian populations. Therefore, the results of this study also supported the hypothesis that a large amount of the gene pool in mainland Japanese was derived from the continental gene flow after the Yayoi Age.

Mitochondrial haplogroup B is negatively associated with elite Korean endurance athlete status

김기철,진한준,김욱 한국유전학회 2012 Genes & Genomics Vol.34 No.5

Mitochondrial DNA (mtDNA) mutations could contribute to aerobic performance, since they provide information to generate aerobic ATP energy by oxidative phosphorylation (OXPHOS) in their respiratory chain. Owing to haploid and absence of recombination, specific mutations in the mtDNA genome associated with human exercise tolerance or intolerance arise and remain in particular genetic lineages referred to as haplogroups. Recent studies have suggested that certain mtDNA lineages were associated with individual differences in trainability and physical capacity, but their origins and replicate test remain to be elucidated. We have therefore analyzed mtDNA haplogroup B variants to assess the possible role of the lineages to differences in elite athletic performance in a population-based case-control study in Cheonan, Korea. We demonstrated a significant negative association between mtDNA haplogroup B and the status of elite endurance athlete [n=378, odds ratio = 0.37 (95% CI: 0.14 - 0.97, p = 0.016)]. Thus, our results imply that specific mtDNA lineages may provide a significant effect on elite Korean endurance status, although larger sample sizes functional studies are necessary to further substantiate these findings.