Estrogen Receptor α Gene Polymorphisms and Peak Bone Density in Chinese Nuclear Families

PBD is an important determinant of osteoporotic fractures. Few studies were performed to search for genes underlying PBD variation in Chinese populations. We tested linkage and/or association of the estrogen receptor α gene polymorphism with PBD in 401 Chinese nuclear families. This study suggests the ER-α gene may have some minor effects on PBM variation in the Chinese population. Low peak bone density (PBD) in adulthood is an important determinant of osteoporotic fractures in the elderly. PBD variation is mainly regulated by genetic factors. Extensive molecular genetics studies have been performed to search for genes underlying PBD variation, largely in whites. Few studies were performed in Chinese populations. In this study, we simultaneously test linkage and/or association of the estrogen receptor α (ER-α) gene polymorphism with PBD in 401 Chinese nuclear families (both parents plus their female children) of 1260 subjects, with the 458 children generally between 20 and 40 years of age. All the subjects were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) at polymorphic PvuII and XbaI sites inside the ER-α gene. Bone mineral density was measured at the lumbar spine (L1-L4) and hip (femoral neck, trochanter, and intertrochanteric region). Raw bone mineral density values were adjusted by age, height, and weight as covariates. We detected marginally significant results for within-family association (transmission disequilibrium; p = 0.054) between the spine bone mineral density variation and the ER-α XbaI genotypes. For the hip bone mineral density variation, significant (p < 0.05) linkage results were generally found for the two intragenic markers. Analyses of the haplotypes defined by the two markers confer further evidence for linkage of the ER-α with the hip PBD variation. In conclusion, this study suggests that the ER-α gene may have minor effects on PBD variation in our Chinese population.link_to_subscribed_fulltex

Paleozoic multiple subduction-accretion processes of the southern Altaids

The formation and development of the southern Altaids is controversial with regard to its accretionary orogenesis and continental growth. The Altay-East Junggar orogenic collage of North Xinjiang, China, offers a special natural laboratory to resolve this puzzle. Three tectonic units were juxtaposed, roughly from North to South, in the study area. The northern part (Chinese Altay), composed of variably deformed and metamorphosed Paleozoic sedimentary, volcanic, and granitic rocks, is interpreted as a Japan-type island arc of Paleozoic to Carboniferous-Permian age. The central part (Erqis), which consists of ophiolitic mélanges and coherent assemblages, is a Paleozoic accretionary complex. The southern part (East Junggar), characterized by imbricated ophiolitic mélanges, Nb-enriched basalts, adakitic rocks and volcanic rocks, is regarded as a Devonian-Carboniferous intra-oceanic island arc with some Paleozoic ophiolites, superimposed by Permian arc volcanism. A plagiogranite from an imbricated ophiolitic mélange (Armantai) in the East Junggar yields a new SHRIMP zircon age of 503 ± 7 Ma. Using published age constraints, we propose the presence of multiple subduction systems in this part of the Paloasian Ocean in the Paleozoic. The intraoceanic arcs became accreted to the southern active margin of the Siberian craton in the middle Carboniferous-Permian. During the long accretionary processes, in addition to large-scale southward-directed thrusting, large-scale, orogen-parallel, strikeslip movements (for example, Erqis fault) in the Permian translated fragments of these intraoceanic arcs and associated accretionary wedges. This new tectonic model has broad implications for the architecture and crustal growth of Central Asia and for other ancient orogens.link_to_subscribed_fulltex

Differentiation of Caucasians and Chinese at bone mass candidate genes: Implication for ethnic difference of bone mass

Bone mineral density (BMD) is an important risk factor for osteoporosis and has strong genetic determination. While average BMD differs among major ethnic groups, several important candidate genes have been shown to underlie BMD variation within populations of the same ethnicity. To investigate whether important candidate genes may contribute to ethnic differences in BMD, we studied the degree of genetic differentiation among several important candidate genes between two major ethnic groups: Caucasians and Chinese. The genetic variability of these two populations (1131 randomly selected individuals) was studied at six restriction sites exhibiting polymorphisms of five important candidate genes for BMD: the BsaHI polymorphism of the calcium-sensing receptor (CASR) gene, the SacI polymorphism of the α 2HS-glycoprotein (AHSG) gene, the PvuII and XbaI polymorphisms of the estrogen receptor α (ESR1) gene, the ApaI polymorphism of the vitamin D receptor (VDR) gene, and the BstBI polymorphism of the parathyroid hormone (PTH) gene. The two ethnic groups showed significant allelic and genotypic differentiation of all the polymorphisms studied. The mean F ST was 0.103, which significantly differed from zero (P < 0.01). The Chinese population had lower mean heterozygosity (0.331) than the Caucasian one (0.444); the CASR-BsaHI and PTH-BstBI polymorphisms contributed most significantly to this difference. Analysis of the intra- and inter-population variability suggests that various types of natural selection may affect the observed patterns of variation at some loci. If some of the candidate genes we studied indeed underlie variation in BMD, their population differentiation revealed here between ethnic groups may contribute to understanding ethnic difference in BMD. © University College London 2003.link_to_subscribed_fulltex

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 1 (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 β 1 (TGF-β 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 χ 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. © Springer-Verlag 2003.link_to_subscribed_fulltex