Soil organic carbon stock and distribution in cultivated land converted to grassland in a subtropical region of China.

Land-use change from one type to another affects soil carbon (C) stocks which is associated with fluxes of CO2 to the atmosphere. The 10-years converted land selected from previously cultivated land in hilly areas of Sichuan, China was studied to understand the effects of land-use conversion on soil organic casrbon (SOC) sequestration under landscape position influences in a subtropical region of China. The SOC concentrations of the surface soil were greater (P\0.001) for converted soils than those for cultivated soils but lower (P\0.001) than those for original uncultivated soils. The SOC inventories (1.90­1.95 kg m-2) in the 0­15 cm surface soils were similar among upper, middle, and lower slope positions on the converted land, while the SOC inventories (1.41­1.65 kg m-2) in this soil layer tended to increase from upper to lower slope positions on the cultivated slope. On the whole, SOC inventories in this soil layer significantly increased following the conversion from cultivated land to grassland (P\0.001). In the upper slope positions, converted soils (especially in 0­5 cm surface soil) exhibited a higher C/N ratio than cultivated soils (P = 0.012), implying that strong SOC sequestration characteristics exist in upper slope areas where severe soil erosion occurred before land conversion. It is suggested that landscape position impacts on the SOC spatial distribution become insignificant after the conversion of cultivated land to grassland, which is conducive to the immobilization of organic C. We speculate that the conversion of cultivated land to grassland would markedly increase SOC stocks in soil and would especially improve the potential for SOC sequestration in the surface soil over a moderate period of time (10 years).

Association analyses of vitamin D-binding protein gene with compression strength index variation in Caucasian nuclear families.

UNLABELLED: This study was conducted to test whether there exists an association between vitamin D-binding protein (DBP) gene and compression strength index (CSI) phenotype. Candidate gene association analyses were conducted in total sample, male subgroup, and female subgroup, respectively. Two single-nucleotide polymorphisms (SNPs) with significant association results were found in males, suggesting the importance of DBP gene polymorphisms on the variation in CSI especially in Caucasian males. INTRODUCTION: CSI of the femoral neck (FN) is a newly developed phenotype integrating information about bone size, body size, and bone mineral density. It is considered to have the potential to improve the performance of risk assessment for hip fractures because it is based on a combination of phenotypic traits influencing hip fractures rather than a single trait. CSI is under moderate genetic determination (with a heritability of approximately 44% found in this study), but the relevant genetic study is still rather scarce. METHODS: Based on the known physiological role of DBP in bone biology and the relatively high heritability of CSI, we tested 12 SNPs of the DBP gene for association with CSI variation in 405 Caucasian nuclear families comprising 1,873 subjects from the Midwestern US. Association analyses were performed in the total sample, male and female subgroups, respectively. RESULTS: Significant associations with CSI were found with two SNPs (rs222029, P = 0.0019; rs222020, P = 0.0042) for the male subgroup. Haplotype-based association tests corroborated the single-SNP results. CONCLUSIONS: Our findings suggest that the DBP gene might be one of the genetic factors influencing CSI phenotype in Caucasians, especially in males.

Genome-wide association analyses suggested a novel mechanism for smoking behavior regulated by IL15.

Cigarette smoking is the leading preventable cause of death in the United States. Although smoking behavior has a significant genetic determination, the specific genes and associated mechanisms underlying the smoking behavior are largely unknown. Here, we carried out a genome-wide association study on smoking behavior in 840 Caucasians, including 417 males and 423 females, in which we examined approximately 380,000 single nucleotide polymorphisms (SNPs). We found that a cluster of nine SNPs upstream from the IL15 gene were associated with smoking status in males, with the most significant SNP, rs4956302, achieving a P-value (8.80 x 10(-8)) of genome-wide significance. Another SNP, rs17354547 that is highly conserved across multiple species achieved a P-value of 5.65 x 10(-5). These two SNPs, together with two additional SNPs (rs1402812 and rs4956396) were selected from the above nine SNPs for replication in an African-American sample containing 1251 subjects, including 412 males and 839 females. The SNP rs17354547 was replicated successfully in the male subgroup of the replication sample; it was associated with smoking quantity (SQ), the Heaviness of Smoking Index (HSI) and the Fagerstrom Test for Nicotine Dependence (FTND), with P-values of 0.031, 0.0046 and 0.019, respectively. In addition, a haplotype formed by rs17354547, rs1402812 and rs4956396 was also associated with SQ, HSI and FTND, achieving P-values of 0.039, 0.0093 and 0.0093, respectively. To further confirm our findings, we carried out an in silico replication study of the nine SNPs in a Framingham Heart Study sample containing 7623 Caucasians from 1731 families, among which, 3491 subjects were males and 4132 were females. Again, the male-specific association with smoking status was observed, for which seven of the nine SNPs achieved significant P-values (P<0.05) and two achieved marginally significant P-values (P<0.10) in males. Several of the nine SNPs, including the highly conserved one across species, rs17354547, are located at potential transcription factor binding sites, suggesting transcription regulation as a possible function for these SNPs. Through this function, the SNPs may modulate the gene expression of IL15, a key cytokine regulating immune function. As the immune system has long been recognized to influence drug addiction behavior, our association findings suggest a novel mechanism for smoking addiction involving immune modulation through the IL15 pathway.

A whole genome linkage scan for QTLs underlying peak bone mineral density.

UNLABELLED: We conducted a whole genome linkage scan for quantitative trait loci (QTLs) underlying peak bone mineral density (PBMD). Our efforts identified several potential genomic regions for PBMD and highlighted the importance of epistatic interaction and sex-specific analyses in identifying genetic regions underlying PBMD variation. INTRODUCTION: Peak bone mineral density (PBMD) is an important clinical risk predictor of osteoporosis and explains a large part of bone mineral density (BMD) variation. METHODS: To detect susceptive quantitative trait loci (QTLs) for PBMD variation including consideration of epistatic and sex-specific effects, we conducted a whole genome linkage scan (WGLS) for PBMD using 2,200 Caucasians from 207 pedigrees, aged 20-50 years. All the individuals were genotyped with 410 microsatellite markers. In addition to WGLS in the total combined sample of males and females, we conducted epistatic interaction analyses, and sex-specific subgroup linkage analyses. RESULTS: We identified several potential genomic regions that met the criteria for suggestive linkage. The most impressing region is 12p12 for hip PBMD (LOD = 2.79) in the total sample. Epistatic interaction analyses found a significant epistatic interaction between 12p12 and 22q13 (p = 0.0021) for hip PBMD. Additionally, we detected suggestive linkage evidence at 15q26 (LOD = 2.93), 2p13 (LOD = 2.64), and Xq27 (LOD = 2.64). Sex-specific analyses suggested the presence of sex-specific QTLs for PBMD variation. CONCLUSIONS: Our efforts identified several potential regions for PBMD and highlighted the importance of epistatic interaction and sex-specific analyses in identifying genetic regions underlying PBMD variation.

Association analysis of vitamin D-binding protein gene polymorphisms with variations of obesity-related traits in Caucasian nuclear families.

BACKGROUND: Vitamin D-binding protein (DBP) gene is well known for its function on glucose and vitamin D metabolism in human populations. Previous studies suggested that the in vivo DBP level may play a role in the etiology of obesity. However, few studies explored the contribution of DBP gene to the variance of obesity phenotypes. OBJECTIVE: To investigate the relationship of DBP polymorphisms and obesity in Caucasian nuclear families. DESIGN: We genotyped 14 single-nucleotide polymorphisms (SNPs) located in and around the DBP gene in 1873 Caucasian subjects from 405 nuclear families. Three obesity-related quantitative phenotypes were investigated, including body mass index (BMI), fat mass and percentage of fat mass (PFM). Single SNPs and haplotypes (three blocks) were tested by family-based association using the FBAT software. RESULTS: SNP2 (rs17467825) and its corresponding haplotype GAA (frequency 0.270) in block 1 showed strongest associations with PFM (P=0.0011 and 0.0023, respectively). In multivariate test significant association was also observed for SNP2 with fat mass&BMI&PFM (P=0.0098). Subsequent sex-stratified analyses demonstrated nominal association for SNP2 and haplotype GAA with PFM in the female subgroup. CONCLUSION: Polymorphisms of DBP gene were significantly association with human PFM, especially in female, suggesting the importance of DBP gene in the pathogenesis of human obesity.

A genomewide scan for quantitative trait loci underlying areal bone size variation in 451 Caucasian families.

BACKGROUND: Bone size is an important determinant of bone strength and is under strong genetic control. OBJECTIVE: To identify quantitative trait loci (QTL) for areal bone size variation, a large-scale genomewide linkage scan was carried out in 451 Caucasian families. PARTICIPANTS AND METHODS: Of 4124 people with phenotypes, 3899 were genotyped with 410 microsatellite markers. Multipoint linkage analyses were carried out in the entire sample, as well as in men and women separately. Potential epistatic interactions between identified genomic regions were also assessed. RESULTS: Several potentially important genomic regions were identified, such as 8q24 for hip bone size (logarithm of the ratio of the odds that two loci are linked (LOD) 3.27) and 2p24 (LOD 2.04) for spine bone size. 8q24 may also interact with 19p13 to affect hip bone size. Several sex-specific QTL were also detected, such as 14q21 (LOD 2.94) for wrist bone size in women and 16q12 (LOD 2.19) for hip bone size in men. CONCLUSIONS: Together with previous findings, this study has further delineated the genetic basis of bone size and laid a foundation for future studies to eventually elucidate the mechanisms of bone size regulation and associated fracture risks.

Ethnic difference in osteoporosis-related phenotypes and its potential underlying genetic determination.

Osteoporosis is a serious health problem in both Caucasians and Asians. Caucasians and Asians are two distinct major ethnic groups, which may have differential genetic determination underlying complex genetic diseases such as osteoporosis. However, to date, there has been no systematic review focusing on the aspect of ethnic difference in risk to osteoporosis and its potential underlying genetic determination between Asians and Caucasians. Here, we firstly review diverse aspects of osteoporosis-related differences, including the differences of epidemiology of osteoporotic fractures, peak bone mass, bone loss, bone area, bone geometry and drug treatment response between Asians and Caucasians. Then, we provide some potential genetic evidence on the different heritability and inheritance mode of bone phenotypes, the different osteoporosis candidate genes and the differential results in related molecular studies between them, to explain the above osteoporosis-related phenotypic differences. The results suggest that the osteoporosis-related phenotypic differences between Asians and Caucasians may be partially the result of the different ethnic genetic background. The present review may increase our understanding of potential different mechanisms related to ethnicity in pathogenesis of osteoporosis for effective and potentially customized treatments in different major ethnic groups.

A survey of haplotype variants at several disease candidate genes: the importance of rare variants for complex diseases.

BACKGROUND: The haplotype based association method offers a powerful approach to complex disease gene mapping. In this method, a few common haplotypes that account for the vast majority of chromosomes in the populations are usually examined for association with disease phenotypes. This brings us to a critical question of whether rare haplotypes play an important role in influencing disease susceptibility and thus should not be ignored in the design and execution of association studies. METHODS: To address this question we surveyed, in a large sample of 1873 white subjects, six candidate genes for osteoporosis (a common late onset bone disorder), which had 29 SNPs, an average marker density of 13 kb, and covered a total of 377 kb of the DNA sequence. RESULTS: Our empirical data demonstrated that two rare haplotypes of the parathyroid hormone (PTH)/PTH related peptide receptor type 1 and vitamin D receptor genes (PTHR1 and VDR) with frequencies of 1.1% and 2.9%, respectively, had significant effects on osteoporosis phenotypes (p = 4.2 x 10(-6) and p = 1.6 x 10(-4), respectively). Large phenotypic differences (4.0 approximately 5.0%) were observed between carriers of these rare haplotypes and non-carriers. Carriers of the two rare haplotypes showed quantitatively continuous variation in the population and were derived from a wide spectrum rather than from one extreme tail of the population phenotype distribution. CONCLUSIONS: These findings indicate that rare haplotypes/variants are important for disease susceptibility and cannot be ignored in genetics studies of complex diseases. The study has profound implications for association studies and applications of the HapMap project.

Vitamin D receptor gene polymorphisms are linked to and associated with adult height.

BACKGROUND: The vitamin D receptor (VDR) gene is important to human stature, as it mediates metabolic pathways, calcium homeostasis, and phosphate homeostasis, which influence growth. METHODS: We examined the relationship between VDR and adult height in 1873 white subjects from 406 nuclear families. Four SNPs, namely -4817A/G at intron 1, FokI C/T at exon 2 start codon, BsmI A/G at intron 8, and TaqI T/C at exon 9 in VDR were tested for linkage and association with adult height variation by the program QTDT (quantitative transmission disequilibrium test). The bT haplotype of the BsmI and TaqI loci was further tested for its association with height in unrelated samples randomly chosen from the 406 nuclear families by traditional population association methods. RESULTS: All four tested SNPs were linked to adult height. Within family associations with height were detected at BsmI and TaqI loci (p = 0.048 and 0.039, respectively). Analyses based on BsmI/TaqI haplotypes also revealed evidence for linkage (p = 0.05) and association (p = 0.001) with height. The bT haplotype was significantly associated with higher adult height (p = 0.033, within family association test). Such an association might be female specific and influenced by menstrual status. CONCLUSIONS: Our results strongly suggest that VDR may be linked to and associated with adult height variation in white populations.

A genome-wide linkage scan for bone mineral density in an extended sample: evidence for linkage on 11q23 and Xq27.

BACKGROUND: Osteoporosis is a major public health problem, mainly quantified by low bone mineral density (BMD). The majority of BMD variation is determined by genetic effects. A pilot whole genome linkage scan (WGS) was previously reported in 53 white pedigrees with 630 subjects. Several genomic regions were suggested to be linked to BMD variation. OBJECTIVE: To substantiate these previous findings and detect new genomic regions. METHODS: A WGS was conducted on an extended sample where the size was almost tripled (1816 subjects from 79 pedigrees). All the subjects were genotyped with 451 microsatellite markers spaced approximately 8.1 cM apart across the human genome. Two point and multipoint linkage analyses were carried out using the variance component method. RESULTS: The strongest linkage signal was obtained on Xq27 with two point LOD scores of 4.30 for wrist BMD, and 2.57 for hip BMD, respectively. Another important region was 11q23, which achieved a maximum LOD score of 3.13 for spine BMD in multipoint analyses, confirming the results on this region in two earlier independent studies. Suggestive linkage evidence was also found on 7p14 and 20p12. CONCLUSIONS: Together with the findings from other studies, the current study has further delineated the genetic basis of bone mass and highlights the importance of increasing sample size to confirm linkage findings and to identify new regions of linkage.

[Prediction of curative effect of amblyopia by laser interference fringe visual acuity].

Laser interference fringe visual acuities (IVAs) and E visual acuities (EVAs) of 116 cases 171 amblyopic eyes were examined. All cases were treated by various therapies and the average follow-up was 2.5 years. Before treatment, the IVAs of 86.5% eyes were better than their EVAs and the IVAs of 13.5% eyes were equal to their EVAs. After treatment, the EVAs of all the eyes were raised to their IVA levels (P < 0.0001, r = 0.8218). The results show that the IVA examination can predict the curative effect and monitor the treatment of amblyopia. The relationships between the IVA and the character of visual fixation, the type and degree of amblyopia, elder child and adult amblyopia, etc. were discussed.