Biomedical subjects

Hong-Wen Deng

Publications and source records attributed to Hong-Wen Deng.

At least 91 records · Page 5Linked to original sources

PubMed2004

High heritability of bone size at the hip and spine in Chinese.

Bone size, an independent determinant of bone strength, is an important risk factor for osteoporotic fracture. In the present study, we investigated the magnitude of the genetic determination of bone size at the spine and hip and their genetic covariation (if any) in a population of Chinese residing in Shanghai City of P.R. China. The subjects were 50 healthy full-sib pairs of females, 188 mother-daughter pairs, and 128 husband-wife pairs selected from 401 nuclear families. Bone size (centimeters squared) was measured at the spine and hip by dual-energy X-ray absorptiometry (DEXA). The narrow-sense heritabilities h2 (SE) of bone size at the spine and hip were 0.63 (0.14) and 0.45 (0.14) respectively when estimated by full-sib pairs, and 0.60 (0.07) and 0.69 (0.07) respectively when estimated by mother-daughter pairs. Marginally significant genetic correlation was observed between the spine and hip bone size. The significantly and moderately high h2 values for bone size demonstrated in this study warrant a subsequent genetic study to search for the genes or genomic regions underlying the phenotype in Chinese.

Absorptiometry, Photon↗

PubMed2004

Bone mineral density in elderly Chinese: effects of age, sex, weight, height, and body mass index.

To enhance our understanding of the relationship between bone mineral density (BMD) and sex, age, body mass index (BMI), weight, and height in elderly Chinese, we studied 258 males aged 50-80 years (mean +/- SD, 62.9 +/- 6.2 years) and 193 females aged 46-75 years (59.0 +/- 6.2 years). We measured BMD at the lumbar spine (L1-L4), hip (femoral neck, trochanter, and intertrochanter), and Ward's triangle. A significant difference of age-adjusted BMD among male-female groups (P < 0.0001) was observed. After adjustment for weight, the magnitude of the sex difference in BMD was reduced at all studied skeletal sites; for example, the difference declined from 18.3% to 5.5% at the spine. There were significant differences in BMD among age-stratified groups at all the sites in both sexes (P < 0.01), except for spine BMD in males (P = 0.928). Regression analysis suggested that, with aging, greater differences of BMD distribution exist in elderly females than in males. Weight accounted for the greatest proportion of age-adjusted BMD variation (e.g., at femoral neck, R(2) = 0.17 in males) among four variables: weight, height, BMI, and a principal component formed from weight and height. These results suggested that weight decreased the sex difference in BMD in elderly Chinese. Patterns of age-related BMD distribution and BMD change among different age groups differed between the sexes and between the studied sites. Weight accounted for most of the effect of two correlated variables (weight and height) on BMD in our sample.

Absorptiometry, Photon↗

PubMed2004

Lack of association between the HindIII RFLP of the osteocalcin (BGP) gene and bone mineral density (BMD) in healthy pre- and postmenopausal Chinese women.

In Caucasian populations, the polymorphic restriction endonuclease HindIII marker of the osteocalcin (also known as BGP, for bone Gla protein) gene has recently been reported to be associated with bone mass, a major risk determinant of osteoporosis. In this study, we investigated the relationship between the BGP HindIII polymorphism and bone mineral density (BMD) in 388 premenopausal (31.18 +/- 5.92 years) and 169 postmenopausal (58.90 +/- 6.27 years) Chinese women. The BMD of spine and hip was measured by dual-energy X-ray absorptiometry (DEXA). All the study subjects were genotyped at the HindIII site of the BGP gene by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) detecting methods. The BGP alleles were designated according to the absence ( H) or presence ( h) of the HindIII restriction site. We did not find any significant difference in spine and hip BMD across BGP genotypes in either pre- or postmenopausal women or the combined group. Our result is not consistent with recent reports that the HindIII marker of the BGP gene is associated with osteoporosis. The different findings may reflect inter-population differences in the association (i.e., linkage disequilibrium) of molecular markers with BMD, and indicate the limit of using the HindIII marker of the BGP gene as a genetic marker to discern women susceptible to low BMD and thus osteoporosis in Chinese.

Adolescent↗

PubMed2004

Test of linkage and/or association between the estrogen receptor alpha gene with bone mineral density in Caucasian nuclear families.

Extensive studies have been performed on the association between the estrogen receptor alpha (ER-alpha) gene and bone mineral density (BMD). Despite considerable efforts, the studies using limited markers and relatively small sample size have yielded largely inconsistent results. In this study, 1873 Caucasian subjects from 405 nuclear families containing 1512 sib pairs were recruited. BMD at the lumbar spine (LS) and femoral neck (FN) was measured by dual-energy X-ray absorptiometry (DXA). Seven single-nucleotide polymorphisms (SNPs) spanning from exon 1 to 8 in the ER-alpha gene were genotyped. The program QTDT (quantitative transmission disequilibrium test) was applied to test linkage and/or association of the ER-alpha gene and BMD variation using individual SNP markers and reconstructed haplotypes. Linkage disequilibrium (LD) was generally detected for SNPs in the ER-a gene (P < 0.05). Associations were observed between SNP rs932477 and FN BMD (P = 0.028), and between the most predominant three-marker haplotype (GCG) containing SNP rs932477 and FN BMD (P = 0.010). Within-family association (present only with both linkage and association) between SNP rs2228480 (G2014A) and FN BMD (P = 0.015) was observed. The most predominant seven-SNP haplotype (TCGCGGG) was associated with higher LS BMD (P = 0.015). However, after correction for multiple testing, these associations did not reach statistical significance. Denser markers may be necessary to better define the relationship between the ER-alpha gene and BMD variation in our sample.

Absorptiometry, Photon↗

PubMed2004

A follow-up linkage study for bone size variation in an extended sample.

Bone size, which has strong genetic determination, is an important determinant of bone strength and a risk factor of osteoporotic fractures. We previously reported an approximately 10-cm genome-wide linkage scan in 630 subjects from 53 US Caucasian pedigrees. The strongest evidence of linkage was obtained on chromosome 17q22 near the marker D17S787, with a two-point LOD score of 3.98 and a multipoint maximum LOD score (MLS) of 3.01. Additionally, suggestive linkages (1.54 < MLS < 2.83) were found at the other four chromosomal regions. In the present study, with an attempt to further examine our previous findings, we perform a follow-up linkage analysis in an expanded sample of 79 pedigrees with 1816 subjects. The total sample contains >80,000 informative relative pairs for linkage analyses, including 3846 sib pairs. Fifteen markers covering the above five promising regions are genotyped, narrowing the average genomic distance from approximately 10 to 5 cm. In the total 79 pedigrees, support of linkage was achieved for the wrist bone size at 17q22 with a two-point LOD score of 2.27 (P = 0.0006) and MLS of 1.78 (P = 0.002). The genomic region 17q22 includes COL1A1, a strong candidate gene that is significantly associated with osteoporotic fracture risk. Our data suggest that this region is promising for further exploratory studies.

Adult↗

PubMed2004

Lack of evidence for a major gene in the Mendelian transmission of BMI in Chinese.

OBJECTIVES: To determine the heritability of BMI and to examine the mode of inheritance of BMI variation in Chinese. RESEARCH METHODS AND PROCEDURES: Familial correlation and complex segregation analyses for BMI were undertaken in a Chinese sample composed of 392 nuclear families, with 1190 total individuals. RESULTS: A moderate heritability was found for BMI (h2 = 0.419-0.492). The obtained results do not support a major gene for BMI in our samples. BMI may be inherited in a complex and non-Mendelian manner in Chinese. DISCUSSION: The findings of this study suggest that identification of specific genes for BMI in Chinese, at least within the same data set, is a serious challenge because of the lack of evidence of a major gene for BMI in our Chinese sample.

Aged↗

PubMed2004

Association between COL1A1 gene polymorphisms and bone size in Caucasians.

Bone size is an important determinant of bone strength and a risk factor of osteoporotic fracture. Several studies indicate that bone size has a high heritability. Thus, a better understanding of genetic factors regulating bone size might have important clinical implications. In the present study, we examined the relationship between the collagen type I alpha 1 (COL1A1) gene and bone size at the spine, hip and wrist in a sample of 1873 subjects of Caucasian origin from 405 nuclear families. Three single-nucleotide polymorphisms (SNPs) in the COL1A1 gene were analyzed. The minor allele frequencies were 15.4, 18.8, and 1.9% for SNP1, SNP2, and SNP3, respectively. Haplotypes were reconstructed based on the family information as well as marker genotypes using the program Genehunter. We did not find evidence of population stratification, within-family association, or linkage for either single SNPs or haplotypes at any skeletal site. Suggestive evidence of total association was observed for the wrist size at SNP2 (P=0.011). After adjusting age, sex, height, and weight, subjects with the T allele of SNP2 had, on average, 3.05% smaller wrist size than noncarriers. When the subjects were divided into families with only female offspring and families with male offspring only, similar total associations were found at the wrist size for SNP2 with P-values of 0.011 and 0.010, respectively. In conclusion, the COL1A1 gene may have some effects on bone size variation at the wrist, but not at the spine or hip in our Caucasian nuclear families.

Adult↗

PubMed2004

Genetic dissection of human stature in a large sample of multiplex pedigrees.

Recently, we reported a whole genome scan on a sample of 630 Caucasian subjects from 53 human pedigrees. Several genomic regions were suggested to be linked to height. In an attempt to confirm the identified genomic regions, as well as to identify new genomic regions linked to height, we conducted a whole genome linkage study on an extended sample of 1,816 subjects from 79 pedigrees, which includes the 53 pedigrees containing the original 630 subjects from our previous whole genome study and an additional 128 new subjects, and 26 further pedigrees containing 1,058 subjects. Several regions achieved suggestive linkage signals, such as 9q22.32 [MLS (multipoint LOD score) = 2.74], 9q34.3 [MLS = 2.66], Xq24 [two-point LOD score = 2.64 at the marker DXS8067], and 7p14.2 [MLS = 2.05]. The importance of the above regions is supported either by other whole genome studies or by candidate genes within these regions relevant to linear growth or pathogenesis of short stature. In addition, this study has tentatively confirmed the Xq24 region's linkage to height, as this region was also detected in the previous whole genome study. To date, our study has achieved the largest sample size in the field of genetic linkage studies of human height. Together with the findings of other studies, the current study has further delineated the genetic basis of human stature.

Adult↗

PubMed2004

A follow-up linkage study for quantitative trait loci contributing to obesity-related phenotypes.

We have recently reported a whole-genome scan in a sample of 630 subjects from 53 extended pedigrees, in which several genomic regions that may contain quantitative trait loci (QTLs) for obesity were suggested. In the present study, with an attempt to confirm our previous findings, we performed a follow-up linkage study in an expanded sample of 79 pedigrees with 1816 subjects (including expanded previous 53 pedigrees and 26 newly recruited pedigrees containing 1058 subjects). A new set of microsatellite markers spanning previously identified regions were selected, with the average genomic distance narrowed from approximately 10 cM to approximately 5 cM in this study. Using a variance component method, we performed two- and multipoint linkage analyses in the following three sample sets: expanded previous 53 pedigrees (758 subjects), 26 new pedigrees, and 79 total pedigrees. For body mass index, analyses of the expanded 53 pedigrees attained a LOD score of 2.32 near marker D1S468 in two-point analysis and a maximum LOD score (MLS) of 2.21 in multipoint analysis; 2q14 near marker D2S347 attained a LOD score of 3.42 in two-point analysis and a MLS of 3.93 in multipoint analysis. The linkage peaks at 1p36 and 2q14 were further supported in the analyses of all 79 pedigrees, with multipoint MLS being 1.38 and 0.90, respectively. For fat mass, genomic region 6q27 achieved a LOD score of 1.24 in two-point analysis and an MLS of 0.92 in multipoint analysis in all 79 pedigrees. Our data support that 1p36, 2q14, and 6q27 are promising regions that may harbor QTLs for obesity phenotypes.

Adult↗

PubMed2003

Interaction effects between estrogen receptor alpha gene, vitamin D receptor gene, age, and sex on bone mineral density in Chinese.

We evaluated the interaction effects between the estrogen receptor alpha gene (ER-alpha), vitamin D receptor gene (VDR), age and sex on bone mineral density (BMD) in a sample of 340 unrelated males and 297 unrelated females from 401 Chinese nuclear families. Polymorphisms of PvuII and XbaI in the ER-alpha gene and ApaI in the VDR gene were detected by RFLP, and ER-alpha genotype was defined by the haplotype reconstructed according to the two loci. In the females, significant ER-VDR gene interaction ( P<0.05) was found on the lumbar spine BMD. Such interaction might account for approximately 1.0% of the BMD variation. At the femoral neck and trochanter, significant ER-age interaction effects were observed, which might explain 0.3% BMD variation for both skeletal sites. In the males, significant VDR-age interaction was found on femoral neck BMD ( P<0.05), and it accounted for 0.6% BMD variation. These interaction effects were largely dependent on gender groups, suggesting there may exist ER-VDR-sex, ER-age-sex, and VDR-age-sex complex interactions in our Chinese sample.

Age Factors↗

PubMed2003

Estrogen receptor alpha and vitamin D receptor gene polymorphisms and bone mineral density: association study of healthy pre- and postmenopausal Chinese women.

In the present study, we tested the association between the estrogen receptor alpha (ER-alpha) and vitamin D receptor (VDR) genes with bone mineral density (BMD). A total of 649 healthy Chinese women, classified as pre-menopausal (N=388) and post-menopausal (N=261) groups, were genotyped at the ER-alpha PvuII, XbaI, and VDR ApaI sites. BMDs at the lumbar spine (L(1)-L(4)) and total hip were measured by dual-energy X-ray absorptiometry. For the VDR ApaI locus, AA carriers had lower spine BMD than Aa (p=0.02) and aa carriers (p<0.01) in the pre-menopausal group. For the ER-alpha gene, carriers of haplotype px had lower spine BMD than the non-carriers (p=0.03) in the pre-menopausal group. Furthermore, we observed significant interaction between the ER-alpha and VDR genes in the post-menopausal group: with AA genotype (or A allele) at the VDR ApaI locus, pX carriers had higher spine BMD than the non-carriers (p=0.02), and PX carriers had lower hip BMD than the non-carriers (p=0.04). Our data suggest that the ER-alpha and VDR genes may be associated with the BMD variation in Chinese women.

Absorptiometry, Photon↗

PubMed2003

Searching for osteoporosis genes in the post-genome era: progress and challenges.

Osteoporosis is a common skeletal disease characterized by low bone mineral density (BMD), deterioration of bone microarchitecture and increased fracture risk. It is a complex disease that has high social and economic costs. Osteoporosis and its associated phenotypes are under the strong genetic control. Identification and characterization of specific loci or genes involved in determining osteoporosis and its associated phenotypes will contribute to a greater understanding of the pathogenesis of osteoporosis, and ultimately might lead to the development of better diagnosis, prevention and treatment strategies. Efforts to identify osteoporosis genes have focused on three approaches: animal models, candidate gene approach, and genome-wide scans. In this article, we review the current status for mapping and identification of genes for osteoporosis, with a focus on some promising regions and future prospects.

Animals↗

PubMed2003

Parathyroid hormone gene with bone phenotypes in Chinese.

Osteoporosis is a common disorder afflicting old people. The parathyroid hormone (PTH) gene is involved in bone remodeling and calcium homeostasis, and has been considered as an important candidate gene for osteoporosis. In this study, we simultaneously tested linkage and/or association of PTH gene with bone mineral density (BMD) and bone mineral content (BMC), two important risk factors for osteoporosis. A sample of 1263 subjects from 402 Chinese nuclear families was used. The families are composed of both parents and at least one healthy daughter aged from 20 to 45 years. All the subjects were genotyped at the polymorphic BstBI site inside the intron 2 of the PTH gene (a nucleotide substitution of G to A at the position +3244). BMD and BMC were measured at the lumbar spine and the hip region via dual-energy X-ray absorptiometry (DXA). Using QTDT (quantitative trait transmission disequilibrium test), we did not find significant results for association or linkage between the PTH gene and BMD or BMC variation at the spine or hip. Our data do not support the PTH gene as a quantitative trait locus (QTL) underlying the bone phenotypic variation in the Chinese population.

Adult↗

PubMed2003

Linkage and association of the CA repeat polymorphism of the IL6 gene, obesity-related phenotypes, and bone mineral density (BMD) in two independent Caucasian populations.

Genetic factors play an important role in osteoporosis and obesity, two serious public health problems in the world. We investigated the relationships between obesity-related phenotypes, bone mineral density (BMD) and the CA repeat polymorphism of the IL6 gene in two large independent samples using the quantitative transmission disequilibrium test (QTDT). The first sample consisted of 1,816 individuals from 79 multigenerational pedigrees. Each pedigree was identified through a proband with BMD Z-scores </=-1.28 at the hip or spine. The second sample was a randomly ascertained set of 636 individuals from 157 nuclear families. Ten alleles containing 9-18 CA repeats were identified in our Caucasian populations. For body mass index (BMI), fat mass and percentage fat mass (PFM), highly significant (P<0.01) or significant (P<0.05) results were found for linkage in our sample of nuclear families and for association in the multigenerational pedigrees. We also observed weak evidence for linkage (P=0.069) with spine BMD and for association with hip BMD in the sample of multigenerational pedigrees. Our results suggest that genetic variation in or near the IL6 locus may be involved in the etiology of obesity and osteoporosis.

Adult↗

PubMed2003

Several genomic regions potentially containing QTLs for bone size variation were identified in a whole-genome linkage scan.

Bone size is an important determinant of osteoporotic fractures. For a sample of 53 pedigrees that contains more than 10,000 relative pairs informative for linkage analyses, we performed a whole-genome linkage scan using 380 microsatellite markers to identify genomic regions that may contain QTLs of bone size (two dimensional measurement by dual energy X-ray absorptiometry). We conducted two- and multi-point linkage analyses. Several potentially important genomic regions were identified. For example, the genomic region 17q23 may contain a QTL for wrist (ultra distal) bone size variation; a LOD score of 3.98 is achieved at D17S787 in two-point analyses and a maximum LOD score (MLS) of 3.01 is achieved in multi-point analyses in 17q23. 19p13 may contain a QTL for hip bone size variation; a LOD score of 1.99 is achieved at D19S226 in two-point analyses and a MLS of 2.83 is achieved in 19p13 in multi-point analyses. The genomic region identified on chromosome 17 for wrist bone size seems to be consistent with that identified for femur head width variation in an earlier whole-genome scan study. The genomic regions identified in this study and an earlier investigation on one-dimensional bone size measurement by radiography are compared. The two studies may form a basis for further exploration with larger samples and/or denser markers for confirmation and fine mapping studies to eventually identify major functional genes and the associated etiology for osteoporosis.

Age Factors↗

PubMed2003

Polymorphisms of four bone mineral density candidate genes in Chinese populations and comparison with other populations of different ethnicity.

Studies on polymorphisms of candidate genes and their association with bone mineral density (BMD) have been reported in many populations, but few have been reported in Chinese populations. We investigated polymorphisms of the following five commonly used markers of four prominent BMD candidate genes with the purpose of identifying useful genetic markers for osteoporosis genetic research in Chinese: the Sp1 and RsaI polymorphisms of the collagen type 1 alpha l (Col1a1) gene, the -174G/C promoter polymorphism of the interleukin 6 (IL-6) gene, the Asn363Ser polymorphism of the glucocorticoid receptor (GR) gene, and the T --> C polymorphism in intron 5 of the transforming growth factor beta(1) (TGF-beta(1)) gene. We evaluated these polymorphisms using PCR-RFLP in samples of at least 124 random individuals. We compared the polymorphisms of these five markers with other populations using the chi(2) test and Fisher's exact two-tailed test. For the RsaI polymorphism, only three heterozygotes but no variant homozygote were identified. For the -174G/C polymorphic site, only one GC heterozygote and no CC homozygote were found. Alleles s, Ser, and A(1) at the Sp1, Asn363Ser, and T --> C marker sites that have been found to be polymorphic in other populations were not found in Chinese. Significant differences of allele and genotype frequency distributions were observed at these polymorphisms ( P < 0.001) after comparing with other populations. Our results suggest that variant alleles of the five markers are absent or too rare to be useful genetic makers in Chinese, despite the fact that they have been commonly used as polymorphic markers in osteoporosis genetic research in other populations.

Base Sequence↗

PubMed2003

LOD score exclusion analyses for candidate QTLs using random population samples.

While extensive analyses have been conducted to test for, no formal analyses have been conducted to test against, the importance of candidate genes as putative QTLs using random population samples. Previously, we developed an LOD score exclusion mapping approach for candidate genes for complex diseases. Here, we extend this LOD score approach for exclusion analyses of candidate genes for quantitative traits. Under this approach, specific genetic effects (as reflected by heritability) and inheritance models at candidate QTLs can be analyzed and if an LOD score is < or = -2.0, the locus can be excluded from having a heritability larger than that specified. Simulations show that this approach has high power to exclude a candidate gene from having moderate genetic effects if it is not a QTL and is robust to population admixture. Our exclusion analysis complements association analysis for candidate genes as putative QTLs in random population samples. The approach is applied to test the importance of Vitamin D receptor (VDR) gene as a potential QTL underlying the variation of bone mass, an important determinant of osteoporosis.

Bone Density↗

PubMed2003

Robust indices of Hardy-Weinberg disequilibrium for QTL fine mapping.

Hardy-Weinberg disequilibrium (HWD) measures have been proposed using dense markers to fine map a quantitative trait locus (QTL) to regions < approximately 1 cM. Earlier HWD measures may introduce bias in the fine mapping because they are dependent on marker allele frequencies across loci. Hence, HWD indices that do not depend on marker allele frequencies are desired for fine mapping. Based on our earlier work, here we present four new HWD indices that do not depend on marker allele frequencies. Two are for use when marker allele frequencies in a study population are known, and two are for use when marker allele frequencies in a study population are not known and are only known in the extreme samples. The new measures are a function of the genetic distance between the marker locus and a QTL. Through simulations, we investigated and compared the fine mapping performance of the new HWD measures with that of the earlier ones. Our results show that when marker allele frequencies vary across loci, the new measures presented here are more robust and powerful.

Chromosome Mapping↗