Biomedical subjects

Hong-Wen Deng

Publications and source records attributed to Hong-Wen Deng.

At least 55 records · Page 3Linked to original sources

PubMed2005

Mapping quantitative trait loci for cross-sectional geometry at the femoral neck.

UNLABELLED: A genome-wide linkage scan was performed in a sample of 79 multiplex pedigrees to identify genomic regions linked to femoral neck cross-sectional geometry. Potential quantitative trait loci were detected at several genomic regions, such as 10q26, 20p12-q12, and chromosome X. INTRODUCTION: Bone geometry is an important determinant of bone strength and osteoporotic fractures. Previous studies have shown that femoral neck cross-sectional geometric variables are under genetic controls. To identify genetic loci underlying variation in femoral neck cross-sectional geometry, we conducted a whole genome linkage scan for four femoral neck cross-sectional geometric variables in 79 multiplex white pedigrees. MATERIALS AND METHODS: A total of 1816 subjects from 79 pedigrees were genotyped with 451 microsatellite markers across the human genome. We performed linkage analyses on the entire data, as well as on men and women separately. RESULTS: Significant linkage evidence was identified at 10q26 for buckling ratio (LOD = 3.27) and Xp11 (LOD = 3.45) for cortical thickness. Chromosome region 20p12-q12 showed suggestive linkage with cross-sectional area (LOD = 2.33), cortical thickness (LOD = 2.09), and buckling ratio (LOD = 1.94). Sex-specific linkage analyses further supported the importance of 20p12-q12 for cortical thickness (LOD = 2.74 in females and LOD = 1.88 in males) and buckling ratio (LOD = 5.00 in females and LOD = 3.18 in males). CONCLUSIONS: This study is the first genome-wide linkage scan searching for quantitative trait loci underlying femoral neck cross-sectional geometry in humans. The identification of the genes responsible for bone geometric variation will improve our knowledge of bone strength and aid in development of diagnostic approaches and interventions for osteoporotic fractures.

Absorptiometry, Photon↗

PubMed2005

Genetic determination and correlation of body mass index and bone mineral density at the spine and hip in Chinese Han ethnicity.

The purpose of the present study was to evaluate the magnitude of genetic determination of spine and hip bone mineral density (BMD) and body mass index (BMI), and to explore the genetic, environmental, and phenotypic correlations among the above phenotypes in Chinese Han ethnicity. The sample was composed of at least 217 complete nuclear families in Chinese Han ethnicity. BMD at the spine and hip was measured using a dual-energy X-ray absorptiometry scanner. The heritability (h2) of BMI and BMD at the spine and hip, the genetic correlation (rhoG) and environmental correlation (rhoE) among the three phenotypes were evaluated via variance analysis, with age, sex, and age-by-sex interaction as covariates. The phenotypic correlation (rhoP) and the bivariate heritability rhoG2 were also calculated. The heritability for BMD and BMI was approximately 0.70 and approximately 0.50, respectively (p<0.0001). The common environment shared by household members (household effect) is significant for BMI variation (p=0.0004). Significant genetic, environmental, and phenotypic correlation was observed. The rhoG2 values were 0.13 for BMI/spine BMD, 0.18 for BMI/hip BMD, and 0.58 for the spine BMD/hip BMD. While BMD at the spine and hip have significant genetic determination, BMI is more likely to be affected by environmental factors than BMD. In addition, BMD at the spine and hip shares more genetic effect (pleiotropy) than BMI and BMD do in Chinese Han ethnicity, though the effects are significant for both.

Adult↗

PubMed2005

Linkage exclusion analysis of two candidate regions on chromosomes 7 and 11: leptin and UCP2/UCP3 are not QTLs for obesity in US Caucasians.

Leptin (LEP) and the uncoupling proteins 2 and 3 (UCP2/UCP3) are key molecules involved in the regulation of food intake and energy expenditure. However, their contribution to variation of obesity phenotypes in the general population remains controversial. The present study is to investigate whether chromosomal regions 7q and 11q, which contain LEP and UCP2/UCP3, respectively, can be excluded for linkage with obesity phenotypes. The obesity phenotypes include body mass index (BMI), fat mass, and percentage fat mass (PFM), with the latter two measured by dual-energy X-ray absorptiometry. We conducted exclusion linkage analyses using a variance component approach in a sample of 1816 individuals coming from 79 extended Caucasian pedigrees. In this study, we were able to exclude chromosomal region 7q containing LEP as having an effect on fat mass and PFM at effect sizes of 5% or greater, and on BMI at effect sizes of 10% or greater. We were able to exclude chromosomal region 11q containing UCP2/UCP3 as having an effect on fat mass and PFM at effect sizes of 10% or greater, and on BMI at effect sizes of 5% or greater. Our results suggest that the LEP and UCP2/UCP3 genes are unlikely to have a substantial effect on variation in obesity phenotypes in this particular US Caucasian population.

Carrier Proteins↗

PubMed2005

A novel pathophysiological mechanism for osteoporosis suggested by an in vivo gene expression study of circulating monocytes.

Bone mineral density (BMD) is a major risk factor for osteoporosis. Circulating monocytes may serve as early progenitors of osteoclasts and produce a wide variety of factors important to bone metabolism. However, little is known about the roles of circulating monocytes in relation to the pathophysiology of osteoporosis. Using the Affymetrix HG-U133A GeneChip(R) array, we performed a comparative gene expression study of circulating monocytes in subjects with high and low BMD. We identified in total 66 differentially expressed genes including some novel as well as some already known to be relevant to bone metabolism. Three genes potentially contributing to bone metabolism, CCR3 (chemokine receptor 3), HDC (histidine decarboxylase, i.e. the histamine synthesis enzyme), and GCR (glucocorticoid receptor), were confirmed by quantitative real-time reverse transcriptase-PCR as up-regulated in subjects with lower BMD. In addition, significant negative correlation was observed between expression levels of the genes and BMD Z-scores. These three genes and/or their products mediate monocyte chemotaxis, histamine production, and/or sensitivity to glucocorticoids. Our results suggest a novel pathophysiological mechanism for osteoporosis that is characterized by increased recruitment of circulating monocyte into bone, enhanced monocyte differentiation into osteoclasts, as well as osteoclast stimulation via monocyte functional changes. This is the first in vivo microarray study of osteoporosis in humans. The results may contribute to identification of new genes and their functions for osteoporosis and suggest genetic markers to discern individuals at higher risk to osteoporosis with an aim for preventive intervention and treatment.

Aged↗

PubMed2005

Bone mineral density and five prominent candidate genes in Chinese men: associations, interaction effects and their implications.

OBJECTIVES: Osteoporosis constitutes a serious health problem in old people. Bone mineral density (BMD) is determined by multiple genetic and environmental factors. The genetic control of BMD and osteoporosis is better understood in women, but much less in men. The present study evaluated the relationship of COL1A2, BGP, IL-6, AHSG and PTH genes defined by MspI, HindIII, BsrBI, SacI and BstBI restriction enzymes, respectively, with BMD in Chinese males. METHODS: A total of 258 unrelated healthy Chinese men aged 50-80 years were recruited. BMD at spine (L1-4) and femoral neck were measured by a Hologic 2000+ densitometer and adjusted by significant covariates of age, height and weight. All the subjects were genotyped at the upper five polymorphic sites by PCR-RFLP procedure. RESULTS: We revealed significant association of the AHSG gene with the spine BMD (P = 0.006), even after adjusting for multiple testing in our study. Carriers of 1*1 and 2*2 genotypes of AHSG gene had, respectively, approximately 5.1 and 8.1% higher spine BMD than those of 1*2 genotype. For the other four genes, no evidence of association was found (P > 0.10). No significant evidence of gene-by-gene interaction was found by two-way factorial ANOVA on the BMD variation. CONCLUSIONS: The results suggest that the AHSG gene is associated with the spine BMD in Chinese men. The present study represents the first effort to simultaneously investigate the effects of single gene locus as well as gene-by-gene interactions of multiple genes on BMD variation in Chinese men.

Age Factors↗

PubMed2005

Association tests of interleukin-6 (IL-6) and type II tumor necrosis factor receptor (TNFR2) genes with bone mineral density in Caucasians using a re-sampling approach.

Interleukin 6 (IL-6) and tumor necrosis factor (TNF) are important cytokines for bone turnover. In this study, a promoter C-174G single-nucleotide polymorphism (SNP) within the IL-6 gene affecting the transcription rate of IL-6 and an exon 6 T676G SNP of the TNF receptor 2 (TNFR2) gene causing an M196R amino-acid change were examined for their relationship with bone mineral density (BMD). Four hundred and five multi-offspring Caucasian families, including 389 male children and 744 female children, were used. One thousand re-samplings were conducted and in each data set, one child was randomly chosen from each family. For each data set, one-way analysis of variance (ANOVA) test was independently implemented using age, age2, sex, height and weight as covariates. There were 523, 288, 204 and 369 significant results out of 1,000-replicate re-samplings of the data of the IL-6 SNP (P<0.05) for one-third, mid-distal, ultradistal radius BMD, and the first principal component (PC1) extracted from the three radial BMDs, respectively, which means that the confidences for associations of the C-174G SNP in the IL-6 gene with one-third, mid-distal, ultradistal radius (totally called distal forearm) BMDs, and PC1, were 52.3, 28.8, 20.4 and 36.9%, respectively. For this SNP with BMD at other skeletal sites and the TNFR2 T676G SNP with BMD at any site, significant results were far less than 200 times out of 1,000 re-sampling replicates. The exceedingly consistent permutation results further improved the confidence of the associations. It may imply that the IL-6 C-174G SNP is associated with distal forearm BMD, but there is no evidence that the TNFR2 T676G SNP is related with BMD in US Caucasians. This is the first attempt to conduct association test utilizing a re-sampling approach. Our results may be more informative than other association analyses that were only based on one sampling result. The results also suggest that different samplings could produce significantly diverse results even for the same population and the results from one sampling are unlikely to be conclusive. Our results have significant implications for association studies and interpretation of non-reproducible association findings.

Body Weights and Measures↗

PubMed2005

Hotelling's T2 multivariate profiling for detecting differential expression in microarrays.

The most widely used statistical methods for finding differentially expressed genes (DEGs) are essentially univariate. In this study, we present a new T(2) statistic for analyzing microarray data. We implemented our method using a multiple forward search (MFS) algorithm that is designed for selecting a subset of feature vectors in high-dimensional microarray datasets. The proposed T2 statistic is a corollary to that originally developed for multivariate analyses and possesses two prominent statistical properties. First, our method takes into account multidimensional structure of microarray data. The utilization of the information hidden in gene interactions allows for finding genes whose differential expressions are not marginally detectable in univariate testing methods. Second, the statistic has a close relationship to discriminant analyses for classification of gene expression patterns. Our search algorithm sequentially maximizes gene expression difference/distance between two groups of genes. Including such a set of DEGs into initial feature variables may increase the power of classification rules. We validated our method by using a spike-in HGU95 dataset from Affymetrix. The utility of the new method was demonstrated by application to the analyses of gene expression patterns in human liver cancers and breast cancers. Extensive bioinformatics analyses and cross-validation of DEGs identified in the application datasets showed the significant advantages of our new algorithm.

Algorithms↗

PubMed2005

The (CA)n polymorphism of the TNFR2 gene is associated with peak bone density in Chinese nuclear families.

Low peak bone density (PBD) in adulthood is an important determinant of osteoporotic fracture (OF) in the elderly. The tumor necrosis factor receptor 2 (TNFR2) gene has been considered as an important candidate gene for PBD due to its important role in bone turnover. In this study, we recruited a total of 1,263 subjects from 402 Chinese nuclear families composed of both parents and at least one daughter, and tested the association of the (CA)(n) polymorphism in intron 4 of the TNFR2 gene with PBD using a more contemporary quantitative transmission disequilibrium test (QTDT). Significant within-family association was detected between the CA16 allele and bone mineral density (BMD) at the lumbar spine with the P-value of 0.005 after permutations, which is still significant after correction for multiple testing. Some evidence of total-family association between the CA16 allele and lumbar spine BMD was found (P=0.021), although the significant level did not reach the empirical threshold (P< or =0.007). About 3.14% of lumbar spine BMD variation can be explained by the CA16 allele. In summary, our results suggest that the TNFR2 gene may play an important role in determining lumbar spine BMD variation in Chinese women.

Bone Density↗

PubMed2005

Linkage and association analyses of the UCP3 gene with obesity phenotypes in Caucasian families.

Uncoupling protein 3 (UCP3) uncouples ATP production from mitochondrial respiration, thereby dissipating energy as heat and affecting the efficiency of energy metabolism. Genetic variations in the UCP3 gene have been conceived to affect body weight in the general population. In this study, using the quantitative transmission disequilibrium test (QTDT), we assessed linkage and association between the UCP3 gene and obesity phenotypes in a large sample of 1,873 subjects from 405 United States Caucasian nuclear families. Obesity phenotypes tested include body mass index (BMI), fat mass, percent fat mass (PFM), and lean mass, with the latter three measured by dual-energy X-ray absorptiometry. We first selected five single nucleotide polymorphisms (SNPs) and then analyzed three highly polymorphic ones, namely, -55 C/T (promoter), Tyr99Tyr (exon 3), and Tyr210Tyr (exon 5), in the total sample. Significant linkage disequilibria (0.392 <or= D' <or= 0.940, P < 0.0001) were observed between pairs of SNPs. In single-locus analyses, we found statistically significant association (P = 0.034) and linkage (P = 0.031) between -55 C/T and BMI. This polymorphism explains 2.29% of BMI variation, and subjects carrying the T allele had an average of 3.5% lower BMI than those without it (P = 0.003). In haplotype analyses, we also observed evidence of linkage (P = 0.002) and association (P = 0.035) with BMI. In summary, our results suggest that UCP3 gene polymorphisms may contribute to BMI variation in this Caucasian population.

Alleles↗

PubMed2005

Genetic and environmental correlations between bone phenotypes and anthropometric indices in Chinese.

Height, weight, bone mineral density (BMD), and bone size are all influenced by genetic and environmental factors as well as interactions between them. Height and weight are often used in population studies to adjust the bone phenotypes. However, it is still unknown what proportion of genetic and environmental variability is shared between these anthropometric characteristics and the bone phenotypes. The genetic and environmental correlations between the bone phenotypes and anthropometric indices in Chinese subjects were studied by bivariate quantitative genetic analysis on a sample of 931 healthy subjects from 292 Chinese nuclear families aged from 19 to 79 years. BMD and bone size at the lumbar spine (L1-L4) and the hip of all subjects were measured by dual-energy X-ray absorptiometry. We found significant genetic correlations between weight and spine BMD, hip BMD, spine bone size and hip bone size, which were 0.50 (P<0.01), 0.45 (P<0.01), 0.36 (P=0.02), and 0.38 (P<0.01), respectively. Likewise, significant genetic correlations between height and spine BMD, spine bone size, and hip bone size were 0.30 (P=0.02), 0.54 (P<0.01), and 0.58 (P<0.01), respectively. The environmental correlations were found to be significant only between height and spine bone size (P<0.001) and weight and hip BMD (P=0.02). These results suggest the probability that the same genetic and environmental factors contribute to these different phenotypes. Moreover, when a candidate gene or genomic region is responsible for the variation of both bone phenotypes and anthropometric indices, its true genetic effect on the bone phenotypes may be lost after one has adjusted the phenotypic values with weight and height as random environmental factors. It may have implications for population studies of candidate genes that underlie the complex bone phenotypes and for the development of strategies for therapeutic application.

Absorptiometry, Photon↗

PubMed2005

Genetic determination of variation and covariation of bone mineral density at the hip and spine in a Chinese population.

Bone mineral density (BMD) is a significant determinant of risk for osteoporosis. Genetic factors are known to account for a major proportion of variation of BMD in Caucasians. However, the degree of genetic determination of BMD in Chinese populations has seldom been investigated. The aim of our study was to investigate the magnitude of the genetic determination of BMD at the spine and hip, and their genetic covariation, in a population of Shanghai city in P. R. China. The subjects consisted of 44 full-sib pairs of females aged 19-43 years, 186 mother-daughter pairs, and 270 nuclear families. For BMD at the spine and hip, the values for narrow-sense heritability h2 (+/-SE) were 0.72+/-0.14 and 0.87+/-0.14, respectively, when estimated by full-sib pairs, and 0.44+/-0.07 and 0.77+/-0.07, respectively, when estimated by mother-daughter pairs. There was a significant genetic correlation r(g) (+/-SE) of BMD between the spine and hip, of 0.97+/-0.01 and 0.76+/-0.04, respectively, when estimated by full-sib pairs and mother-daughter pairs. The common household impact on BMD in our study was negligible according to the statistical estimate. We conclude that genetic factors play a major role in the determination of the variation and covariation of BMD at the spine and hip in our Chinese sample.

Adult↗

PubMed2005

Association and linkage analyses of interleukin-6 gene 634C/G polymorphism and bone phenotypes in Chinese.

In this study, we tested the interleukin-6 (IL-6) gene as an important candidate gene for its linkage and association with the variation of bone phenotypes (bone mineral density [BMD] and bone size) in young Chinese female subjects. We genotyped the IL-6 gene at the -634C/G restriction fragment length polymorphism (RFLP) site (ID, RS1800796) in 1263 individuals from 402 Chinese nuclear families, composed of both parents and at least one healthy daughter (mean age +/- SD, 31.4 +/- 5.8 years). Using the daughters' bone phenotypes, we tested total-family association, within-family association (via transmission disequilibrium test, [TDT]), and linkage, between the -634C/G marker and bone phenotypes at the spine and the hip. No significant association or linkage was found for bone size and BMD, although a trend was observed for linkage between the IL-6 gene -634C/G marker and L1-4 spinal BMD (adjusted for age, weight, and height). Our results, together with the findings from other studies, indicate that the IL-6 gene, although important for postmenopausal bone loss, may have a limited impact on peak bone mass variation in a Chinese population.

Adult↗

PubMed2005

The VDR, COL1A1, PTH, and PTHR1 gene polymorphisms are not associated with bone size and height in Chinese nuclear families.

We tested the relationship of the ApaI, Eco31I, BstBI, and (AAAG)n polymorphisms in the vitamin D receptor (VDR), collagen type I alpha-1 (COL1A1), parathyroid hormone (PTH), and parathyroid hormone (PTH)/PTH-related peptide receptor (PTHR1) genes with variations in bone size (BS) and height. Population stratification, total-family association, and within-family association were used to test these relationships in 400 Chinese nuclear families with a total of 1256 individuals. The BS at hip and spine was measured using a Hologic QDR 2000 dual-energy X-ray absorptiometry (DXA) scanner. The minor allele frequencies were 29.2%, 36.0%, and 14.0% for the VDR-ApaI, COL1A1-Eco31I, and PTH-BstBI markers, respectively. (AAAG)5 and (AAAG)6 of the PTHR1 gene are two major alleles in the Chinese people. Significant population stratification was found between the spine BS and PTHR1-(AAAG)5 (P = 0.048) and PTHR1-(AAAG)6 (P = 0.023), as well as between PTHR1-(AAAG)5 and height (P = 0.048), but we did not detect any significant within-family association or total-family association between the VDR, COL1A1, PTH, and PTHR1 gene polymorphisms and the variations in BS and height in our sample. Our results do not support that the VDR, COL1A1, PTH, and PTHR1 genes have an important influence on the variation in BS and height in our Chinese population.

Absorptiometry, Photon↗

PubMed2005

Association and haplotype analyses of the COL1A2 and ER-alpha gene polymorphisms with bone size and height in Chinese.

Bone size (BS) is another risk factor of fracture independent of BMD in determining bone strength, and height is highly related with BS. To test the effect of the estrogen receptor-alpha (ER-alpha) and collagen type I alpha 2 (COL1A2) genes on the variation of BS and height, we genotyped the PvuII and XbaI polymorphisms in the intron 1 of the ER-alpha gene and the MspI and (GT)n markers in the intron 47 and intron 1 of the COL1A2 gene in 400 Chinese nuclear families with a total of 1256 individuals. The BS at the hip and spine was measured using a Hologic QDR 2000 dual-energy X-ray absorptiometry (DXA) scanner. Population stratification, total-family association, and within-family association were used to test the relationship of BS (at the spine and hip) and height with the four polymorphisms. We also performed these association analyses with the haplotypes of the MspI and (GT)n polymorphisms in the COL1A2 gene, and with the haplotypes of the PvuII and XbaI markers in the ER-alpha gene. Weak within-family association was found between the COL1A2-MspI (P = 0.05) and the femoral neck BS, between the ER-alpha-PX (P = 0.04) and the intertrochanter BS, and between the COL1A2-(GT)(17) (P = 0.02), COL1A2-m(GT)(17) (P = 0.009) and height. Subsequent permutation tests generally confirmed the suggestive within-family association. For the weak within-family association, the proportions of phenotypic variance accounted by the COL1A2-MspI, ER-alpha-PX, COL1A2-(GT)(17), COL1A2-m(GT)(17) markers were 1.50%, 1.51%, 2.15%, and 2.43% for the corresponding phenotypes. The association results indicate that the (GT)n and MspI markers of COL1A2 gene may have some influence on the variation of both BS and height, and the XbaI and PvuII markers of ER-alpha gene may have some effect on the variation of height in Chinese but not on the variation of BS.

Adult↗

PubMed2005

No major effect of the insulin-like growth factor I gene on bone mineral density in premenopausal Chinese women.

Osteoporosis is a major public health problem, mainly characterized by low bone mineral density (BMD). BMD is a complex trait that is determined by multiple genes. Insulin-like growth factor I (IGF-I) is an important growth factor of bone and thus IGF-I gene has been considered as an attractive candidate gene for osteoporosis. A few studies on the relationship between variants of the IGF-I gene and BMD variation, via traditional association and/or linkage methods, have yielded conflicting results. In this study, we simultaneously tested association and/or linkage of a cytosine-adenine (CA) repeat polymorphism at 1 kb upstream of the transcription initiation site of the IGF-I gene with BMD variation in a large cohort of premenopausal Chinese women. A total of 1263 subjects from 402 Chinese nuclear families were examined. Each family consists of both parents and at least one daughter aged between 20 and 45 years. BMDs (g/cm(2)) at the lumbar spine and hip were measured using dual-energy X-ray absorptiometry (DXA). Applying the QTDT (quantitative transmission disequilibrium tests) progam, we did not find significant evidence of association or linkage between the CA repeat polymorphism of the IGF-I gene and BMD variation at any skeletal site. Our data do not support the IGF-I gene having major effect on BMD variation in premenopausal Chinese women.

Alleles↗

PubMed2005

Absence of linkage to 8q23.3-q24.1 and 2p11.1-q12.2 in a new BAFME pedigree in China: indication of a third locus for BAFME.

Benign adult familial myoclonic epilepsy (BAFME) were mapped on chromosome 8q24 and 8q23.3-q24.1 in Japanese pedigrees and mapped on 2p11.1-2q12.2 in European pedigrees, respectively. Recently, we recruited a large BAFME pedigree in China. After genotyping 11 microsatellite markers covering the two previously identified chromosome regions, we performed linkage analyses. However, evidence of negative linkage was found in the two previously reported candidate regions (LOD score <-3.0 at no recombination). Our data suggest that the causative gene responsible for BAFME in the Chinese pedigree may be located on a new region other than 8q23.3-q24.1 and 2p11.1-q12.2, indicating the presence of a third locus for BAFME.

Adult↗

PubMed2005

Association between VDR ApaI polymorphism and hip bone mineral density can be modified by body mass index: a study on postmenopausal Chinese women.

Osteoporosis is a major public health problem for old people. Genetic factors are considered to be major contributors to the pathogenesis of postmenopausal osteoporosis. The vitamin D receptor (VDR) gene is a prominent candidate gene for the regulation of postmenopausal bone mass; however, despite extensive studies, controversy remains regarding its association with postmenopausal body mineral density (BMD) variation. In this study, a total of 260 healthy postmenopausal Chinese women were genotyped at the VDR ApaI locus using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). Raw hip BMD was significantly associated with VDR ApaI polymorphism with and without adjusting for age (P=0.015 and 0.040, respectively). This genetic effect can explain 3.32% of hip BMD variation. However, the significant association vanished after correcting for both age and body mass index (BMI) (P=0.169). In addition, we observed a significant association between VDR ApaI polymorphism with unadjusted BMI (P=0.042) or BMI adjusted for age (P=0.049). The raw hip BMD was also found to be significantly correlated with BMI (r=0.517, P=0.0001), with BMI explaining 26.35% of the variation of hip BMD. All of these facts prompt us to conclude that the significant association between the VDR ApaI genotype and hip BMD may be modified by BMI in postmenopausal Chinese women. Our findings may partially explain the earlier inconsistent association results concerning the VDR gene and BMD, and highlight the importance of incorporating covariates such as BMI into osteoporosis association studies.

Aged↗

PubMed2005

Interaction effects between estrogen receptor alpha and vitamin D receptor genes on age at menarche in Chinese women.

AIM: To evaluate whether estrogen receptor alpha (ER-alpha) and vitamin D receptor (VDR) genes are associated with the age at menarche in Chinese women. METHODS: A total of 390 pre-menopausal Chinese women were genotyped at the ER-alpha PvuII, XbaI, and VDR ApaI loci using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). RESULTS: Neither the ER-alpha gene nor the VDR gene individually had significant effects on the age at menarche in our subjects (P>0.10). However, evidence of interaction effects between the two genes were observed: with the aa genotype at the VDR ApaI locus, subjects with haplotype PX at the ER-alpha gene had, on average, 6 months later onset of menarche than the non-carriers (P=0.01). CONCLUSION: We found that neither the ER-alpha gene or the VDR gene had a significant association with the age at menarche individually. However, potential interaction effects between the two genes were observed in Chinese women.

Adult↗