Single nucleotide polymorphisms in bone turnover-related genes in Koreans: ethnic differences in linkage disequilibrium and haplotype.
BACKGROUND
Osteoporosis is defined as the loss of bone mineral density that leads to bone fragility with aging. Population-based case-control studies have identified polymorphisms in many candidate genes that have been associated with bone mass maintenance or osteoporotic fracture. To investigate single nucleotide polymorphisms (SNPs) that are associated with osteoporosis, we examined the genetic variation among Koreans by analyzing 81 genes according to their function in bone formation and resorption during bone remodeling.


METHODS
We resequenced all the exons, splice junctions and promoter regions of candidate osteoporosis genes using 24 unrelated Korean individuals. Using the common SNPs from our study and the HapMap database, a statistical analysis of deviation in heterozygosity depicted.


RESULTS
We identified 942 variants, including 888 SNPs, 43 insertion/deletion polymorphisms, and 11 microsatellite markers. Of the SNPs, 557 (63%) had been previously identified and 331 (37%) were newly discovered in the Korean population. When compared SNPs in the Korean population with those in HapMap database, 1% (or less) of SNPs in the Japanese and Chinese subpopulations and 20% of those in Caucasian and African subpopulations were significantly differentiated from the Hardy-Weinberg expectations. In addition, an analysis of the genetic diversity showed that there were no significant differences among Korean, Han Chinese and Japanese populations, but African and Caucasian populations were significantly differentiated in selected genes. Nevertheless, in the detailed analysis of genetic properties, the LD and Haplotype block patterns among the five sub-populations were substantially different from one another.


CONCLUSIONS
Through the resequencing of 81 osteoporosis candidate genes, 118 unknown SNPs with a minor allele frequency (MAF) > 0.05 were discovered in the Korean population. In addition, using the common SNPs between our study and HapMap, an analysis of genetic diversity and deviation in heterozygosity was performed and the polymorphisms of the above genes among the five populations were substantially differentiated from one another. Further studies of osteoporosis could utilize the polymorphisms identified in our data since they may have important implications for the selection of highly informative SNPs for future association studies.
Kim
Kyung-Seon
KS
Center for Genome Science, National Institute of Health, 5 Nokbun-dong, Eunpyung-gu, Seoul 122-701, Republic of Korea. kskim1997@empal.com
Kim
Ghi-Su
GS
Hwang
Joo-Yeon
JY
Lee
Hye-Ja
HJ
Park
Mi-Hyun
MH
Kim
Kwang-joong
KJ
Jung
Jongsun
J
Cha
Hyo-Soung
HS
Shin
Hyoung Doo
HD
Kang
Jong-Ho
JH
Park
Eui Kyun
EK
Kim
Tae-Ho
TH
Hong
Jung-Min
JM
Koh
Jung-Min
JM
Oh
Bermseok
B
Kimm
Kuchan
K
Kim
Shin-Yoon
SY
Lee
Jong-Young
JY
D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D044383:Black People; D015519:Bone Density / Q000235:genetics*; D016723:Bone Remodeling / Q000235:genetics*; D016022:Case-Control Studies; D002874:Chromosome Mapping; D030561:Databases, Nucleic Acid; D005260:Female; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D007723:Korea; D015810:Linkage Disequilibrium / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000208:ethnology* / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D012044:Regression Analysis; D017422:Sequence Analysis, DNA; D044465:White People