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The article presents the study conducted regarding the role of progesterone receptor (PGR) gene in endometrial cancer risk development in China. The study which collected DNA samples and information from Shanghai Endometrial Cancer Study aims to determine the association of PGR with the cancer risk in the Chinese population. The result shows that the gene is associated with the risk due to the polymorphism in the PGR region.

The article discusses the Shanghai Endometrial Cancer Study of genetic variation in China which aims to investigate the associations with endometrial cancer susceptibility. The study chooses haplotype-tagging single nucleotide polymorphism from Han Chinese data from the HapMap Project and applies the Hardy-Weinberge equilibrium. It discovers that no SNP varies from the Hardy-Weinberge equilibrium and observes no associations between matrix metallproteinase.

The article discusses a study which characterizes genetic variation across the matrix metalloproteinase-2 gene and evaluates the associations with breast cancer risk. Of the 6,066 Chinese women, about 39 of them were genotyped under the Shanghai Breast Cancer Study. It discovers that a rare haplotype reduced the risk of breast cancer, while rare allele homozygotes increased the risk of the cancer.

The article provides information on a study concerning the connectivity between the epidermal growth factor receptor (EGFR) gene polymorphism and the risk of breast cancer among cancer patients in China. According to the article, EGFR gene has been overexpressed in various cancer cases. Meanwhile, its overexpression has been studied and assessed in the cases of breast cancer. Furthermore, its role in breast cancer has not yet proven.

The article presents a study which aims to investigate the connection between the risk of acquiring endometrial cancer and thymidylate synthase (TYMS) gene among the citizens in China. Researchers have used population-based case control study of this type of cancer and the participants were interviewed. DNA samples have also collected from the participants to determine the link. Moreover, researchers have determined the relation between TYMS and endometrial cancer in women.

Abstract Purpose  To investigate the role of alpha2–HS glycoprotein (AHSG) gene on bone mineral density (BMD) variation. Methods  A total of 665 subjects from 157 Caucasian nuclear families were genotyped at the AHSG NlaIII, SacI sites. The association and linkage between the single SNP markers and haplotypes constructed by two markers in this gene and BMDs at the spine and hip were determined by using quantitative transmission disequilibrium test (QTDT). Results  Significant within-family associations were obtained for spine BMD at both of studied markers (P = 0.036 and 0.005 at the NlaIII and SacI sites, respectively). Significant (P = 0.008 at the NlaIII locus) (P = 0.004 at the SacI locus) total associations at spine BMD were detected. Haplotype analyses confirmed those within-family and total association. Conclusions  These data suggest the polymorphisms in the AHSG gene may have effects on BMD variation in Caucasian population. [ABSTRACT FROM AUTHOR]

This study aimed to examine the genetic determination of body weight, body mass index (BMI) and cross-sectional geometric parameters of the femoral neck including cross-sectional area (CSA), cortical thickness (CT), sectional modulus (Z), and buckling ratio (BR), and to test the genetic correlation between body weight/BMI and the femoral neck geometric parameters. A total of 929 healthy subjects from 292 Chinese nuclear families was included. Femoral neck geometric parameters were estimated from bone mineral density (BMD) and bone area which were measured by dual energy X-ray absorptiometry (DXA). The heritability ( h 2) estimate values were 0.643, 0.626, 0.626, 0.674, 0.405, and 0.615 for body weight, BMI, CSA, CT, Z, and BR, respectively. Body weight was significantly correlated with bone geometric parameters ( p≤0.001) with genetic correlation ( ρ G ) values of 0.551, 0.457, 0.571, and −0.385, and bivariate heritability % MathType!Translator!2!1!AMS LaTeX.tdl!TeX -- AMS-LaTeX! % MathType!MTEF!2!1!+- % feaaeaart1ev0aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbbjxAHX % garmWu51MyVXgatuuDJXwAK1uy0HwmaeHbfv3ySLgzG0uy0Hgip5wz % aebbnrfifHhDYfgasaacH8qrps0lbbf9q8WrFfeuY-Hhbbf9v8qqaq % Fr0xc9pk0xbba9q8WqFfea0-yr0RYxir-Jbba9q8aq0-yq-He9q8qq % Q8frFve9Fve9Ff0dmeaabaqaciGacaGaaeqabaWaaeWaeaaakeaada % qadaqaaiabeg8aYnaaDaaaleaacaWGhbaabaGaaGOmaaaaaOGaayjk % aiaawMcaaaaa!3C98! $${\left( {\rho ^{2}_{G} } \right)}$$ values of 0.304, 0.209, 0.326, and 0.148 for CSA, CT, Z, and BR, respectively. Similar correlations ( p≤0.001) were observed between BMI and bone geometric parameters, with ρ G values of 0.446, 0.432, 0.334, and −0.362, and % MathType!Translator!2!1!AMS LaTeX.tdl!TeX -- AMS-LaTeX! % MathType!MTEF!2!1!+- % feaaeaart1ev0aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbbjxAHX % garmWu51MyVXgatuuDJXwAK1uy0HwmaeHbfv3ySLgzG0uy0Hgip5wz % aebbnrfifHhDYfgasaacH8qrps0lbbf9q8WrFfeuY-Hhbbf9v8qqaq % Fr0xc9pk0xbba9q8WqFfea0-yr0RYxir-Jbba9q8aq0-yq-He9q8qq % Q8frFve9Fve9Ff0dmeaabaqaciGacaGaaeqabaWaaeWaeaaakeaacq % aHbpGCdaqhaaWcbaGaam4raaqaaiaaikdaaaaaaa!3B05! $$\rho ^{2}_{G}$$ values of 0.199, 0.187, 0.112, and 0.131 for CSA, CT, Z, and BR, respectively. In summary, our study suggested that body weight, BMI, and femoral neck geometry were under strong genetic determination. The strong genetic correlations suggested that the genetic factors of bone geometry may be overlapped with those of body weight and BMI. [ABSTRACT FROM AUTHOR]

Human height is an important and heritable trait. Our previous two genome-wide linkage studies using 630 (WG1 study) and an extended sample of 1,816 Caucasians (WG2 study) identified 9q22 [maximum LOD score (MLS)=2.74 in the WG2 study] and preliminarily confirmed Xq24 (two-point LOD score=1.91 in the WG1 study, 2.64 in the WG2 study) linked to height. Here, with a much further extended large sample containing 3,726 Caucasians, we performed a new genome-wide linkage scan and confirmed, in high significance, the two regions’ linkage to height. An MLS of 4.34 was detected on 9q22 and a two-point LOD score of 5.63 was attained for Xq24. In an independent sub-sample (i.e., the subjects not involved in the WG1 and WG2 studies), the two regions also achieved significant empirical P values (0.002 and 0.004, respectively) for “region-wise” linkage confirmation. Importantly, the two regions were replicated on a genotyping platform different from the WG1 and WG2 studies (i.e., a different set of markers and different genotyping instruments). Interestingly, 9q22 harbors the ROR2 gene, which is required for growth plate development, and Xq24 was linked to short stature. With the largest sample from a single population of the same ethnicity in the field of linkage studies for complex traits, our current study, together with two previous ones, provided overwhelming evidence substantiating 9q22 and Xq24 for height variation. In particular, our three consecutive whole genome studies are uniquely valuable as they represent the first practical (rather than simulated) example of how significant increase in sample size may improve linkage detection for human complex traits. [ABSTRACT FROM AUTHOR]

Parathyroid hormone/parathyroid hormone-related peptide receptor type 1 (PTHR1) plays an important role in calcium metabolism. It was previously shown to influence variation in bone mineral density (BMD). To investigate its importance in a typical U.S. Caucasian population, we tested linkage or association of the PTHR1 gene with BMD and height. Altogether, 1873 subjects from 405 Caucasian nuclear families were studied. BMD was measured at the lumbar spine (L1–L4) and total hip (femoral neck, trochanter, and intertrochanter regions). Four single nucleotide polymorphisms (SNPs) in the PTHR1 gene were genotyped. Sixteen haplotypes were reconstructed. Only two major haplotypes had frequencies >3% and were thus used for the analysis. Analyses were performed for BMD and height in the total sample and for peak BMD (PBMD) achieved in offspring subjects aged 20–50 in a subsample of 387 nuclear families. We found suggestive evidence for total association between haplotype 13 (AATG) and hip PBMD (P = 0.031). For height, evidence of within-family association was suggested for SNP1, SNP2, and haplotype 4 (GGCA) (P ≰ 0.05). Our findings suggest that the PTHR1 gene may be important for PBMD, height variation, or both, although the significance is dampened by correction for multiple testing. [ABSTRACT FROM AUTHOR]

Estrogen receptor alpha (ER-α) plays an important role in mediating estrogen signaling. Studies in Caucasian populations have shown that it is involved in endocrine-related diseases such as osteoporosis and obesity. In the present study, we first used a quantitative transmission disequilibrium test (QTDT) to examine the relationship between this gene and both the osteoporosis-related phenotype bone mineral density (BMD), and the obesity-related phenotype body mass index (BMI), in 384 Chinese nuclear families. We genotyped a dinucleotide repeat marker (TA) n, and a long-range haplotype was reconstructed using this marker and two other restriction fragment length polymorphism (RFLP) markers at PvuII and XbaI loci. Although we found significant total association [allele (TA)21 with hip BMD ( P=0.001), and haplotype Px(TA)21 with spine ( P=0.0007) and hip ( P=0.0006) BMD], the more reliable within-family associations were not significant between these phenotype pairs. No linkage signal was obtained for either spine BMD or hip BMD. We found no association or linkage between any of the three studied polymorphisms and the long-range haplotypes of the ER-α gene and BMI. Our study does not support an association of the ER-α gene with BMD and BMI in the Chinese population. [ABSTRACT FROM AUTHOR]

To evaluate whether estrogen receptor α(ER-α) and vitamin D receptor (VDR) genes are associated with the age at menarche in Chinese women. A total of 390 pre-menopausal Chinese women were genotyped at the ER-α PvuII, X baI, and VDR ApaI loci using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). Neither the ER-αgene 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-αgene had, on average, 6 months later onset of menarche than the non-carriers ( P=0.01). We found that neither the ER-αgene 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. [ABSTRACT FROM AUTHOR]

Abstract 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 rg (±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. [ABSTRACT FROM AUTHOR]

Low bone mineral density (BMD) is one of the most important risk factors for osteoporosis. Apolipoprotein E (APOE) has been considered as a candidate gene for osteoporosis because of its influence on osteoblast uptake of lipoprotein-borne vitamin K. Using the quantitative transmission disequilibrium test QTDT, we examined linkage and/or association of APOE and BMD at the lumbar spine and the total hip in a sample of 387 Caucasian nuclear families with 715 parents and 953 children. The children were aged 20-50 years and female offspring were premenopausal as well. Four single nucleotide polymorphisms (SNP1-4) in the APOE gene, 4-locus haplotypes and 2-locus haplotypes (e1, e2, e3, e4 isoforms, reconstructed by SNP3 and SNP4) were analyzed. In the whole sample and the female offspring families we found no evidence of linkage or association for either single SNP or haplotype with BMD at the two studied skeletal sites. In the male offspring families, within-family associations were observed at the haplotypesCGTC(P= 0.001),GGTT(P= 0.002), andGATC(P= 0.006) for the lumbar spine BMD, andGATC(P= 0.008) for the total hip BMD. These data suggested that in our studied Caucasian population, APOE may have effects on BMD variation in males but not females. Further studies with a larger sample size are required to confirm such results. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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.European Journal of Human Genetics (2004) 12, 383-388. doi:10.1038/sj.ejhg.5201152 Published online 14 January 2004 [ABSTRACT FROM AUTHOR]

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 h[sup 2] (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 h[sup 2] 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. [ABSTRACT FROM AUTHOR]

Background: Public SNP databases are frequently used to choose SNPs for candidate genes in the association and linkage studies of complex disorders. However, their utility for such studies of diseases with ethnic-dependent background has never been evaluated. Results: To estimate the accuracy and completeness of SNP public databases, we analyzed the allele frequencies of 41 SNPs in 10 candidate genes for obesity and/or osteoporosis in a large American-Caucasian sample (1,873 individuals from 405 nuclear families) by PCR-invader assay. We compared our results with those from the databases and other published studies. Of the 41 SNPs, 8 were monomorphic in our sample. Twelve were reported for the first time for Caucasians and the other 29 SNPs in our sample essentially confirmed the respective allele frequencies for Caucasians in the databases and previous studies. The comparison of our data with other ethnic groups showed significant differentiation between the three major world ethnic groups at some SNPs (Caucasians and Africans differed at 3 of the 18 shared SNPs, and Caucasians and Asians differed at 13 of the 22 shared SNPs). This genetic differentiation may have an important implication for studying the well-known ethnic differences in the prevalence of obesity and osteoporosis, and complex disorders in general. Conclusion: A comparative analysis of the SNP data of the candidate genes obtained in the present study, as well as those retrieved from the public domain, suggests that the databases may currently have serious limitations for studying complex disorders with an ethnic-dependent background due to the incomplete and uneven representation of the candidate SNPs in the databases for the major ethnic groups. This conclusion attests to the imperative necessity of large-scale and accurate characterization of these SNPs in different ethnic groups. [ABSTRACT FROM AUTHOR]

The article discusses a study which investigated the relationship of 23 single-nucleotide polymorphisms (SNP) in insulin-like growth factor (IGF)-I and IGF-II genes with the risk of developing breast cancer. The study included patients from the Shanghai Breast Cancer Study, a case-control study of breast cancer prevalence in Shanghai, China. It concluded that IGF-I or IGF-II genes may not influence breast cancer risk in Chinese women.

Certain polyphenols inhibit the activity of aromatase, a critical enzyme in estrogen synthesis that is coded by the CYP19A1 gene. Consumption of polyphenol-rich foods and beverages, thus, may interact with CYP19A1 genetic polymorphisms in the development of endometrial cancer. The authors tested this hypothesis in the Shanghai Endometrial Cancer Study (1997–2003), a population-based case-control study of 1,204 endometrial cancer cases and 1,212 controls. Dietary information was obtained by use of a validated food frequency questionnaire. Genotypes of CYP19A1 at rs28566535, rs1065779, rs752760, rs700519, and rs1870050 were available for 1,042 cases and 1,035 controls. Unconditional logistic regression models were used to calculate odds ratios and their 95% confidence intervals after adjustment for potential confounding factors. Higher intake of soy foods and tea consumption were both inversely associated with the risk of endometrial cancer, with odds ratios of 0.8 (95% confidence interval: 0.6, 1.0) for the highest versus the lowest tertiles of intake of soy and 0.8 (95% confidence interval: 06, 0.9) for ever tea consumption. The association of single nucleotide polymorphisms rs1065779, rs752760, and rs1870050 with endometrial cancer was modified by tea consumption (pinteraction CYP19A1 genetic polymorphisms on the development of endometrial cancer. [ABSTRACT FROM AUTHOR]