Identification of Two Sex-Specific Quantitative Trait Loci in Chromosome 11q for Hip Bone Mineral Density in Chinese

ArticleinHuman Heredity 61(4):237-43 · February 2006with5 Reads
DOI: 10.1159/000095216 · Source: PubMed
Chromosome 11q has not only been found to contain mutations responsible for the several Mendelian disorders of the skeleton, but it has also been linked to bone mineral density (BMD) variation in several genome-wide linkage studies. Furthermore, quantitative trait loci (QTL) affecting BMD in inbred mice and baboons have been mapped to a region syntenic to human chromosome 11q. The aim of the present study is to determine whether there is a QTL for BMD variation on chromosome 11q in the Chinese population. Nineteen microsatellite markers were genotyped for a 75 cM region on 11q13-25 in 306 Chinese families with 1,459 subjects. BMD (g/cm(2)) was measured by DXA. Linkage analyses were performed using the variance component linkage analysis method implemented in Merlin software. For women, a maximum LOD score of 1.62 was achieved at 90.8 cM on 11q21 near the marker D11S4175 for femoral neck BMD; LOD scores greater than 1.0 were observed on 11q13 for trochanter BMD. For men, a maximum LOD score of 1.57 was achieved at 135.8 cM on 11q24 near the marker D11S4126 for total hip BMD. We have not only replicated the previous linkage finding on chromosome 11q but also identified two sex-specific QTL that contribute to BMD variation in Chinese women and men.
    • "The activity of GSTP1, a phase II metabolizing enzyme, directly related with the clinical feature of fluorosis [30] . Chromosome QTL 11q12-13, where the GSTP1 gene is located, has been associated with variation of bone mineral density (BMD)4041 and osteoporosis-pseudogliomasyndrome, a disorder affecting skeletal strength and vision [42]. The GSTP1 rs1695 SNP, which located within the active site of the enzyme, alters the substrate specificity, activity and thermostability of the GSTP enzyme [2,3132. "
    [Show abstract] [Hide abstract] ABSTRACT: Brick tea type fluorosis is a public health concern in the north-west area of China. The association between SNPs of genes influencing bone mass and fluorosis has attracted attention, but the association of SNPs with the risk of brick-tea type of fluorosis has not been reported.To investigate the modifying roles of GSTP1 rs1695 polymorphisms on this association.A cross-sectional study was conducted. Brick-tea water was tested by the standard of GB1996-2005 (China). Urinary fluoride was tested by the standard of WS/T 89-2006 (China). Skeletal fluorosis was diagnosed by X-ray, the part we scheduled was forearm, shank, and pelvic, then diagnosed the skeletal fluorosis by the standard of WS/192-2008 (China). Gene polymorphism was tested by Sequenom MassARRAY system.The prevalence rate in different ethnical participants was different: Tibetan individuals had the highest prevalence rate of skeletal fluorosis. There were significant differences in genotype frequencies of GSTP1 Rs1695 among different ethnical participants (p
    Full-text · Article · Jun 2015
    • "The dCG cohort also included both men and women, while our HKSC cohort included only women. Since sex-specific genetic architecture has been well demonstrated for BMD variation111213, this difference likely accounts for some differences in the findings. Although the number of subjects in the HKSC cohort was fewer, the HKSC cohort captured information from the extreme 25% (cases, lowest 10%; super control, highest 15%) of 3,200 subjects. "
    [Show abstract] [Hide abstract] ABSTRACT: Gene-based association approach could be regarded as a complementary analysis to the single SNP association analysis. We meta-analyzed the findings from the gene-based association approach using the genome-wide association studies (GWAS) data from Chinese and European subjects, confirmed several well established bone mineral density (BMD) genes, and suggested several novel BMD genes. The introduction of GWAS has greatly increased the number of genes that are known to be associated with common diseases. Nonetheless, such a single SNP GWAS has a lower power to detect genes with multiple causal variants. We aimed to assess the association of each gene with BMD variation at the spine and hip using gene-based GWAS approach. We studied 778 Hong Kong Southern Chinese (HKSC) women and 5,858 Northern Europeans (dCG); age, sex, and weight were adjusted in the model. The main outcome measure was BMD at the spine and hip. Nine genes showed suggestive p value in HKSC, while 4 and 17 genes showed significant and suggestive p values respectively in dCG. Meta-analysis using weighted Z-transformed test confirmed several known BMD genes and suggested some novel ones at 1q21.3, 9q22, 9q33.2, 20p13, and 20q12. Top BMD genes were significantly associated with connective tissue, skeletal, and muscular system development and function (p < 0.05). Gene network inference revealed that a large number of these genes were significantly connected with each other to form a functional gene network, and several signaling pathways were strongly connected with these gene networks. Our gene-based GWAS confirmed several BMD genes and suggested several novel BMD genes. Genetic contribution to BMD variation may operate through multiple genes identified in this study in functional gene networks. This finding may be useful in identifying and prioritizing candidate genes/loci for further study.
    Full-text · Article · Sep 2011
    • "Koller et al. [13] also found linkage of femoral neck BMD and 11q region (LOD 1.15), even so the LOD score had decreased from theirs previous report [16]. This study was also replicated in Chinese women (LOD = 1.62) [17]. These studies suggest chromosome 1q and 11q regions as the regions which can harbor bone maintenance/formation genes. "
    [Show abstract] [Hide abstract] ABSTRACT: To investigate linkage to chromosome 1q and 11q region for lumbar spine, femoral neck and total body BMD and volumetric BMD in Brazilian sister adolescents aged 10-20-year-old and 57 mothers. We evaluated 161 sister pairs (n=329) aged 10-20 years old and 57 of their mothers in this study. Physical traits and lifestyle factors were collected as covariates for lumbar spine (LS), femoral neck (FN) and total body (TB) BMD and bone mineral apparent density (BMAD). We selected nine microsatellite markers in chromosome 1q region (spanning nearly 33cM) and eight in chromosome 11q region (spanning nearly 34cM) to perform linkage analysis. The highest LOD score values obtained from our data were in sister pairs LS BMAD analysis. Their values were: 1.32 (P<0.006), 2.61 (P<0.0002) and 2.44 (P<0.0004) in D1S218, D1S2640 and D1S2623 markers, respectively. No significant LOD score was found with LS and FN BMD/BMAD in chromosome 11q region. Only TB BMD showed significant linkage higher than 1.0 for chromosome 11q region in the markers D11S4191 and D11S937. Our results provided suggestive linkage for LS BMAD at D1S2640 marker in adolescent sister pairs and suggest a possible candidate gene (LHX4) related to adolescent LS BMAD in this region. These results reinforce chromosome 1q21-23 as a candidate region to harbor one or more bone formation/maintenance gene. In the other hand, it did not repeat for chromosome 11q12-13 in our population.
    Full-text · Article · Jul 2011
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