Auranofin inhibits the occurrence of colorectal cancer by promoting mTOR-dependent autophagy and inhibiting epithelial-mesenchymal transformation.

Colorectal cancer (CRC) is one of the world's most common and deadly cancers. According to GLOBOCAN2020's global incidence rate and mortality estimates, CRC is the third main cause of cancer and the second leading cause of cancer-related deaths worldwide. The US Food and Drug Administration has approved auranofin for the treatment of rheumatoid arthritis. It is a gold-containing chemical that inhibits thioredoxin reductase. Auranofin has a number of biological activities, including anticancer activity, although it has not been researched extensively in CRC, and the mechanism of action on CRC cells is still unknown. The goal of this research was to see how Auranofin affected CRC cells in vivo and in vitro . The two chemical libraries were tested for drugs that make CRC cells more responsive. The CCK-8 technique was used to determine the cell survival rate. The invasion, migration, and proliferation of cells were assessed using a transwell test and a colony cloning experiment. An electron microscope was used to observe autophagosome formation. Western blotting was also used to determine the degree of expression of related proteins in cells. Auranofin's tumor-suppressing properties were further tested in a xenograft tumor model of human SW620 CRC cells. Auranofin dramatically reduced the occurrence of CRC by decreasing the proliferation, migration, and invasion of CRC cells, according to our findings. Through a mTOR-dependent mechanism, auranofin inhibits the epithelial-mesenchymal transition (EMT) and induces autophagy in CRC cells. Finally, in-vivo tests revealed that auranofin suppressed tumor growth in xenograft mice while causing no harm. In summary, auranofin suppresses CRC cell growth, invasion, and migration. Auranofin inhibits the occurrence and progression of CRC by decreasing EMT and inducing autophagy in CRC cells via a mTOR-dependent mechanism. These findings suggest that auranofin could be a potential chemotherapeutic medication for the treatment of human CRC.

Effects of bacteria on early-stage litter decomposition in Wudalianchi volcanic forest.

To understand the role of microorganisms in litter decomposition and nutrient cycling in volcanic forest ecosystem, we conducted in-situ litterbag decomposition experiment and used Illumina MiSeq high-throughput sequencing to analyze the response of bacterial community structure and diversity during the decomposition of litters from Larix gmelinii, Betula platyphylla and Populus davidiana, the dominant tree species in volcanic lava plateau of Wudalianchi. The results showed that mass remaining percentage of litters of three species after 18-month decomposition was 63.9%-68.1%. Litter of B. platyphylla decomposed the fastest, with significant difference in N, C:N, and N:P before and after decomposition. The richness of bacterial species and diversity index differed significantly among the three litters. Proteobacteria, Actinomycetes, and Bacteroidetes were the dominant bacterial groups at the phylum level, while Rhizobium, Sphingomonas, and Pseudomonas were the dominant groups at the genus level, with significant difference among the three litters. After 18 months, the dominant bacterial groups in litter tended to be consistent with those in volcanic lava platform soil. In the volcanic forest ecosystem, bacterial diversity and community structure were mainly affected by P, C:N, and N:P in the litter.

[Effects of water levels in heterogeneous habitats on sexual reproductive allocation of Deyeuxia angustifolia.] / å¼‚è´¨ç”Ÿå¢ƒæ°´ä½å·®å¼‚å¯¹å°å¶ç« æœ‰æ€§ç¹æ®–åˆ†é çš„å½±å“.

Taking Deyeuxia angustifolia as the research object, a representative plant of wetland in Sanjiang Plain, we analyzed the variations of individual size and biomass among the habitats of swamp wetlands, swampy meadows, typical meadows and miscellaneous grass meadows, and the relationship between reproductive components and plant biomass. We explored the effects of water level on individual biomass and reproductive allocation of D. angustifolia in different types of wetlands. The results showed that plant biomass, height and the characteristics of sexual reproduction significantly decreased with the increases of water level. The reproductive thresholds of D. angustifolia in miscellaneous grass meadow, typical meadow, swampy meadow, and swamp wetland were 0.245, 0.149, 0.148 and 0.157 g, respectively. There was a significantly negative correlation between plant size and reproductive allocation in three habitats except swampy meadow. Compared with individual size, soil water content had a stronger effect on reproductive allocation of D. angustifolia. The different investment between individual size and reproductive allocation in different habitats was the basic condition that contributes to the good ecological adaptability of D. angustifolia.

[Expression and regulation of the SOST gene].

Sclerostin(SOST), mainly expressed in osteocytes, is a negative regulator of bone formation. Hormones PTH and E2 inhibit the expression of the SOST gene. Transcription factors Osterix, Runx2, and Mef2c promote the SOST expression, while Sirt1 negatively regulates the SOST expression. In addition, the expression of the SOST gene is regulated by epigenetic mechanisms, such as DNA methylation and microRNA. Mutations in the SOST gene, which cause sclerosteosis and Van Buchem diseases, are associated with osteoporosis. Wnt and BMP are two important signaling pathways in bone metabolic regulation. SOST can regulate osteoblastic differentiation and bone formation by binding type I/II receptors and co-receptor LRP5/6 to inhibit BMP and Wnt signaling pathways. Suppression of SOST provides a new approach for osteoporosis treatment. This review covers the structure, function and expression regulation of the SOST gene, human disease association, mechanism in the regulation of bone metabolism and prospect in clinical application.

Identification of genes for bone mineral density variation by computational disease gene identification strategy.

We previously used five freely available bioinformatics tools (Prioritizer, Geneseeker, PROSPECTR and SUSPECTS, Disease Gene Prediction, and Endeavour) to analyze the thirteen well-replicated osteoporosis susceptibility loci and identify a subset of most likely candidate osteoporosis susceptibility genes (Huang et al. in J Hum Genet 53:644-655, 2008). In the current study, we experimentally tested the association between bone mineral density (BMD) and the 9 most likely candidate genes [LAMC2(1q25-q31), MATN3(2p24-p23), ITGAV(2q31-q32), ACVR1(2q23-q24), TDGF1(3p21.31), EGF(4q25), IGF1(12q22-q23), ZIC2(13q32), BMP2(20p12)] which were pinpointed by 4 or more bioinformatics tools. Forty tag SNPs in nine candidate genes were genotyped in a southern Chinese female case-control cohort consisting of 1643 subjects. Single- and multi-marker association analyses were performed using logistic regression analysis implemented by PLINK. Potential transcription factor binding sites were predicted by MatInspector. The strongest association was observed between rs10178256 (MATN3) and trochanter (P < 0.001) and total hip BMD (P = 0.002). The SNP rs6214 (IGF1) showed consistent association with BMD at all the four measured skeletal sites (P = 0.005-0.044). Prediction of transcription factor binding suggested that the minor allele G of rs10178256 might abolish the binding of MESP1 and MESP2 which play vital roles in bone homeostasis, whereas the minor allele G of rs6214 might create an additional binding site for XBP1, a constitutive regulator of endoplasmic reticulum stress response. Our data suggested that variants in MATN3 and IGF1 were involved in BMD regulation in southern Chinese women.

Identification of QTL genes for BMD variation using both linkage and gene-based association approaches.

Low bone mineral density (BMD) is a risk factor for osteoporotic fracture with a high heritability. Previous large scale linkage study in Northern Chinese has identified four significant quantitative trait loci (QTL) for BMD variation on chromosome 2q24, 5q21, 7p21 and 13q21. We performed a replication study of these four QTL in 1,459 Southern Chinese from 306 pedigrees. Successful replication was observed on chromosome 5q21 for femoral neck BMD with a LOD score of 1.38 (nominal p value = 0.006). We have previously identified this locus in a genome scan meta-analysis of BMD variation in a white population. Subsequent QTL-wide gene-based association analysis in 800 subjects with extreme BMD identified CAST and ERAP1 as novel BMD candidate genes (empirical p value of 0.032 and 0.014, respectively). The associations were independently replicated in a Northern European population (empirical p value of 0.01 and 0.004 for CAST and ERAP1, respectively). These findings provide further evidence that 5q21 is a BMD QTL, and CAST and ERAP1 may be associated with femoral neck BMD variation.

Bone mineral density is linked to 1p36 and 7p15-13 in a southern Chinese population.

Genome-wide linkage scans have identified a number of quantitative trait loci (QTLs) affecting bone mineral density (BMD), mainly in the Caucasian population. In this study, we aim to determine whether seven well-replicated QTLs also contribute to BMD variation in the southern Han Chinese population. Thirty-three microsatellite markers in the proximity of seven QTLs were genotyped in 1,459 subjects from 306 families ascertained through a proband with BMD Z-score equal to or less than -1.3 at either the lumbar spine or hip. Regression-based multipoint linkage analysis was performed. In the entire study population, good linkage evidence of total hip BMD to 7p14 [maximum log of odds (LOD) score (MLS) = 2.75; nominal P = 0.0002] and 1p36 (MLS = 1.6, P = 0.003) was revealed. In the subgroup analysis of 1,166 female subjects, MLS of 3.42, 2.65, 2.42, and 1.54 were obtained on 7p12 for total hip, lumbar spine, trochanter, and femoral neck BMD, respectively. A suggestive linkage signal was achieved at 7p14-15 with a MLS of 3.38 and 3.15 for trochanter and total hip BMD in the 678 premenopausal women, and at 7p12 for femoral neck and total hip BMD with MLS of 2.22 and 3.04 in postmenopausal women. Subgroup analysis of premenopausal women also provided additional evidence of suggestive linkage of total hip BMD to 1p36, with a MLS of 2.84 at 17.07 cM. Thus, linkage of BMD to 1p36 and 7p15-13 is confirmed in southern Chinese. Computational prioritization strategy and published genome-wide association studies suggested RERE and SFRP4 as two promising candidate genes in which variants responsible for the linkage signal may be identified by follow-up gene-wide association studies.

[Meta-analysis of LPL Pvuâ ¡ polymorphism with hyperlipoidemia and coronary heart disease in the Chinese population.].

Multiple studies reported the association of LPL PvuⅡpolymorphism (rs285) with hyperlipoidemia and coronary heart disease in the Chinese population; however, the sample sizes of these studies were small (119-647) and the results were not consistent. A Meta-analysis was undertaken to evaluate the role of LPL PvuⅡpolymorphism in hyperlipoidemia and coronary heart disease in Chinese. A total of 11 case-control studies were collected. Among them, 6 studies on hyperlipoidemia contained 943 cases and 1,093 controls, and 5 studies on coronary heart disease contained 821 cases and 727 controls. No significant publication bias was found and significant heterogeneity between these studies was observed. The results of Meta-analysis indicated that the allele P+ increased the risk of hyperlipoidemia (OR=1.36, 95%CI 1.07~1.73, P=0.011), and no evidence of association (P=0.755) was found for coronary heart disease. Our study suggested that the LPL PvuⅡpolymorphism was significantly associated with hyperlipoidemia but not with coronary heart disease in the Chinese population.

[Association and meta-analysis of ENPP1 K121Q with type 2 diabetes in Han Chinese.].

Multiple meta-analyses in Europeans showed that ENPP1 K121Q polymorphism was associated with type 2 diabetes. However, no association in Japanese, Korean, and Chinese in Taiwan, and inconsistent results in mainland Chinese were reported. In this study, the single nucleotide polymorphism K121Q of the ENPP1gene was genotyped in 539 type 2 diabetes patients and 404 healthy controls. No difference was observed in the genotypic and alle-lic frequencies of ENPP1 K121Q between the cases and the controls. Logistic regression analysis with adjustment of sex, age, and BMI suggested that the XQ genotype was significantly associated with the risk of type 2 diabetes (OR=1.5, 95%CI: 1.39-1.62, P<0.001). Sub-group analysis by gender revealed that the association between ENPP1 K121Q and type 2 diabetes was observed only in women (Q: 12.4% vs. 6.1%, P=0.001; XQ: 23.7% vs. 11.7%, P=0.001). Our results suggest that the association of ENPP1 K121Q with type 2 diabetes in Hubei Han Chinese population is more evident in women. The first meta-analysis of 10 Chinese studies indicated that the Q allele increased the risk of type 2 diabetes (OR=1.42, P=0.042).

[Association of the D358A polymorphism of IL6R gene with type 2 diabetes in Hubei Han Chinese].

OBJECTIVE: To investigate the association of the D358A polymorphism of interleukin 6 receptor( IL6R ) gene with type 2 diabetes mellitus (T2DM) in Hubei Han Chinese. METHODS: The single nucleotide polymorphism D358A of the IL6R gene was genotyped in 581 T2DM patients and 353 healthy controls. Meta-analysis was used to assess the reported association between the IL6R D358A and T2DM. RESULTS: The frequencies of CC genotype and C allele of IL6R D358A in the patients were significantly lower than those in controls (CC: 13.4% vs. 20.7%, P=0.003; C: 36.0% vs. 41.8%, P=0.012), with the CC genotype being a protective factor for T2DM (OR=0.595, P=0.003). Logistic regression analysis suggested that the CC genotype was significantly associated with T2DM after adjusted for age, sex, blood pressure and obesity (OR=0.615, 95% CI: 0.407- 0.928, P=0.021). Meta-analysis of 6 studies indicated that there existed genetic heterogeneity, and the CC genotype was associated with lower risk of T2DM (P=0.009, OR=0.64, 95% CI: 0.48-0.85). CONCLUSION: IL6R is a susceptibility gene for T2DM in Han Chinese population of Hubei, and the CC genotype may serve as a genetic protective factor of T2DM.

[Computational biology strategy for identification of complex disease genes].

For the past two decades, the dominant methods to identify susceptibility genes of complex disease were linkage analysis and association study. Linkage analysis usually identifies broad intervals, which can encompass dozens to hundreds of candidate genes. Transition from quantitative trait loci to gene has been a challenge due to the absence of complete functional information for the majority of genes in this susceptibility locus and limited knowledge of the link between gene function and disease. Recently, computational biology tools that employ information extracted from public online databases have been developed. In this review, we introduced principles of DGP, GeneSeeker, Prioritizer, PROSPECTR and SUSPECTS (P and S), and Endeavor, then used the prediction of susceptibility genes for type 2 diabetes mellitus/obesity and osteoporosis as examples to elucidate the application of computational biology strategies, and finally discuss the limitations and prospects of these methods.

Multiple osteoporosis susceptibility genes on chromosome 1p36 in Chinese.

INTRODUCTION: Chromosome 1p36 is a region that has previously shown good evidence of linkage to bone mineral density (BMD) in multiple studies, but the genes that are responsible for the linkage signals are unknown. MATERIALS AND METHODS: We performed a gene-wide and tag SNP-based association study of four positional and functional candidate genes (TNFRSF1B, PLOD, CNR2, and MTHFR) at 1p36 in 1, 243 case-control Chinese subjects. Twenty-three tag SNPs were selected and genotyped using the high-throughput Sequenom genotyping platform. Binary logistic regression analyses were performed to test for genotype associations between each SNP and BMD. Allelic and haplotype association analyses were conducted by Haploview. Gene-gene interactions were investigated using multifactor dimensionality reduction method. RESULTS: The PLOD rs7529452 (C385T; F98F) and MTHFR rs1801133 (C677T; A429E) showed significant genotypic/allelic associations with BMDs at all sites measured (P=0.08-0.001), and a promising two-locus gene-gene interaction for femoral neck BMD. The CNR2 rs2501431 (A592G; G155G) showed nominally significant allelic associations with trochanter and hip BMD. The TNFRSF1B rs976881 showed genotypic associations with BMDs (P=0.08-0.04). CONCLUSIONS: Our results suggest that multiple genes at 1p36, individually or in different combinations, contribute to osteoporosis susceptibility in Chinese.

The -9247 T/C polymorphism in the SOST upstream regulatory region that potentially affects C/EBPalpha and FOXA1 binding is associated with osteoporosis.

Accumulating evidence shows that genes that cause monogenic diseases also contribute to similar complex disease in the general population. We sought to determine whether the allelic variation in seven monogenic bone disease genes (CLCN7, TCIRGI, SOST, CA2, CSTK, TGFB1 and SLC26A2) contributes to osteoporosis/bone mineral density (BMD) variation in the normal Chinese population. We conducted a gene-wide tag SNP-based association study in 1243 Chinese subjects with low BMD (Z-scores < or = -1.28, equivalent to the lowest 10% of the population) and high BMD (Z-score > or = +1.0). Twenty-two tag SNPs were selected and genotyped by using the high-throughput Sequenom genotyping platform. Allelic and haplotype association tests were conducted by Haploview and binary logistic regression analyses. The -9247 polymorphism rs1230399 in the upstream regulatory region of the sclerostin gene showed significant genotypic/allelic associations with spine, femoral neck, trochanter and total hip BMD (P=0.03-0.004). The T-allele of rs1230399 increased the risk of osteoporosis (OR=1.52, P=0.005). Computational analysis showed that rs1230399 is located at the core consensus recognition site of two cooperating transcription factors C/EBPalpha and FOXA1 that modulate estrogen receptor function. T-->C polymorphism abolishes the binding of both C/EBPalpha and FOXA1 to the sclerostin gene. Our data suggest a mechanistic link between rs1230399 and BMD through estrogen ERalpha/FOXA1 signaling pathways driven by long-distance enhancers.

Pre-B-cell leukemia homeobox 1 (PBX1) shows functional and possible genetic association with bone mineral density variation.

Bone mineral density (BMD) is one of the major determinants of risk for osteoporotic fracture. Multiple studies reveal that peak bone mass is under strong genetic influence. One of the major susceptibility loci for peak spine BMD has been mapped to chromosome 1q21-q23 in the Caucasian population. We have previously replicated this finding in Southern Chinese pedigrees and detected a maximum multipoint log of odds (LOD) score of 2.36 in this region. To further fine-map this region, 380 single-nucleotide polymorphic (SNP) markers were genotyped in 610 sibpairs from 231 families. Several markers were identified in the association analysis as important candidates underlying BMD variation. Among them, successful replication was demonstrated for SNPs in pre-B-cell leukemia homeobox 1 (PBX1) gene in two other unrelated case-control cohorts. The functional role of PBX1 in bone metabolism was examined in vitro using human bone-derived cells (HBDC) and murine MC3T3-E1 pre-osteoblasts. PBX1 mRNA was constitutively expressed in both HBDC and MC3T3-E1 cells. Immunostaining revealed that PBX1 is localized in the nucleus compartment. Silencing of PBX1 by RNAi in MC3T3-E1 cells decreased the expression of Runx2 and Osterix, the critical transcription factors for osteogenesis, but accelerated cell proliferation and bone nodule formation. Overall, our data suggest a genetic and functional association of PBX1 with BMD.

[Association studies of the APM1 SNP T45G with type 2 diabetes in Han population of Hubei Province].

To investigate the association between the APM1 SNP rs 13061862 and type 2 diabetes mellitus (T2DM), a total of 603 Han subjects from Hubei Province were genotyped for the APM1 SNP T45G. Both family-based case- control and unrelated case-control designs were used. The frequencies of the G allele and GG genotype for T2DM patients were significantly higher than those for controls (G: 42.0% vs. 21.7%, P<0.001; GG: 13.6% vs. 4.5%, P= 0.032) in all subjects. The GG genotype was associated with higher risk of T2DM in family-based case-control groups (GG: 17.8% vs. 5.6%, P = 0.011), while the G allele and GG genotype for T2DM patients were significantly higher than those for controls in the unrelated case-control groups (GG: 12.2% vs. 3.9%, P = 0.025). Logistic regression analysis suggested that GG genotype was the genetic risk factors for T2DM (OR = 3.58, 95% CI = 1.70-7.54). In conclusion, the APM1 SNP T45G is associated with T2DM risk, and the GG genotype may be a genetic risk factor of T2DM in Han population of Hubei Province.

Prediction of osteoporosis candidate genes by computational disease-gene identification strategy.

Osteoporosis is a complex disease with a strong genetic component. To date, more than 20 genome-wide linkage scans across multiple populations have been launched to hunt for osteoporosis susceptibility genes. Some significant or suggestive chromosomal regions of linkage to bone mineral density have been identified and replicated in genome-wide linkage screens. However, identification of key candidate genes within these confirmed regions is challenging. We used five freely available bioinformatics tools (Prioritizer, GeneSeeker, PROSPECTR and SUSPECTS, Disease Gene Prediction, and Endeavor) to analyze the 13 well-replicated osteoporosis susceptibility loci: 1p36, 1q21-25, 2p22-24, 3p14-25, 4q25-34, 6p21, 7p14-21, 11q14-25, 12q23-24, 13q14-34, 20p12, 2q24-32, and 5q12-21. Pathways and regulatory network analyses were performed using the Ingenuity Pathways Analysis (IPA) software. We identified a subset of most likely candidate osteoporosis susceptibility genes that are largely involved in transforming growth factor (TGF)-beta signaling, granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling, axonal guidance signaling, peroxisome proliferator-activated receptor (PPAR) signaling, and Wnt/beta-catenin signaling pathway. Six nonoverlapping networks were generated by IPA 5.0 from 88 out of the 91 candidate genes. The list of most likely candidate genes and the associated pathway identified will assist researchers in prioritizing candidate disease genes for further empirical analysis and understanding the pathogenesis of osteoporosis.

[Association study between PPARGC1A Thr394Thr/ Gly482Ser polymorphisms and type 2 diabetes].

To investigate the association between single nucleotide polymorphisms (SNPs) rs2970847(Thr394Thr) and rs8192678(Gly482Ser) of peroxisome proliferators activated receptor gamma coactivator-1(PPARGC1A)gene and type 2 diabetes in Chinese Han population in Hubei. The Thr394Thr and Gly482Ser polymorphisms of the PPARGC1A gene were genotyped in 307 controls and 344 type 2 diabetes patients. Single marker/haplotype association analyses and logistic re-gression analysis were performed. Significant differences in genotypic and allelic frequencies were observed between cases and controls for the Thr394Thr polymorphism (genotype, P=0.006; allele, Plt;0.001). The genotype AA of the Thr394Thr polymorphism and the haplotype Thr394(ACA)- Ser482 were significantly associated with type 2 diabetes. No differences in the genotypic and allelic frequencies between cases and controls were found for the Gly482Ser polymorphism. PPARGC1A is a susceptibility gene for type 2 diabetes in Chinese Han population in Hubei.

Association of low-density lipoprotein receptor-related protein 5 (LRP5) promoter SNP with peak bone mineral density in Chinese women.

OBJECTIVE: Low-density lipoprotein receptor-related protein 5 (LRP5) is important for osteoblast differentiation and mutations of the gene are associated with both low and high bone mass syndromes. Our study aimed to evaluate the importance of LRP5 in the determination of peak bone mass acquisition in Chinese females in the general population. METHODS: A total of 286 young southern Chinese females (aged 22-44 years) with low bone mineral density (BMD) (defined by a BMD Z score < or =-1.28 at either the hip or spine) or high BMD (Z score > or =+1) were studied. The LRP5 gene was sequenced for single nucleotide polymorphisms (SNPs) and 4 SNPs were tagged from 8 genotyped SNPs for this study. RESULTS: Single locus allele association tests revealed significant associations of rs682429 and rs686921 with BMD variation (p < 0.05). Omnibus test (likelihood ratio test) revealed overall significant association between LRP5 gene locus and total hip BMD, with rs682429 being most predictive. rs682429 is located in 5'UTR, 2 bases adjacent to a consensus recognition site for the Elk-1 binding element. CONCLUSION: Common variations of the LRP5 promoter are associated with BMD in young women. These significant associations appear to be driven by rs682429. Functional studies are necessary to elucidate the role of this SNP on the effect of Elk-1 binding element transcriptional activity of LRP5 gene.

[Association of Hind RFLP in lipoprotein lipase gene with type 2 diabetes].

We examined the association of a Hind RFLP (restriction fragment length polymorphism) in the lipoprotein lipase (LPL) gene with type 2 diabetes (T2DM) in Chinese Han population in Hubei Province. Genotypes were determined by PCR-RFLP in 102 controls and 264 T2DM patients using sib-pair and unrelated case-control designs. The frequencies of the H+ allele and H+H+ genotype for patients were significantly higher than those for controls (H+: 76.9% vs 69.1%, P < 0.05; H+H+: 59.8% vs 52%, P < 0.05). When all subjects were grouped as designed, the H+ allele and H+H+ genotype for sib patients were significantly higher than those for sib controls (H+: 81.5% vs 67.8%, P < 0.05; H+H+: 68.5% vs 50.7%, P < 0.05), while there were no significant differences in controls and random patients (P>0.05). Logistic regression analysis suggested that risk factors for T2DM was fasting plasma glucose and LPL genotypes, with individuals with the H+H+ genotype doubling their risk for T2DM as compared to those with the H+H- and H-H- genotypes (95% CI: 1.0363.840, P < 0.05). These data suggest that the Hind RFLP in the LPL gene is associated with T2DM risk in Chinese Han population in Hubei Province, and the H+ allele may serve as a genetic risk factor of T2DM.

The association of common polymorphisms in the QPCT gene with bone mineral density in the Chinese population.

Evidence of the linkage of chromosome 2p to bone mineral density (BMD) has previously been reported in multiple populations. However, the identification of the BMD quantitative trait loci (QTL) gene at chromosome 2p remains a challenge. We performed a gene-wide and tag single nucleotide polymorphism (SNP)-based association study of four positional and functional candidate genes (CALM2, CYP1B1, QPCT, and POMC) in a sample of 1,243 cases and matched controls. Thirteen HapMap tag SNPs were selected and genotyped by using the high-throughput Sequenom genotyping platform. Binary logistic regression analyses were performed to test for associations between each SNP genotype and BMD. Haplotype association analyses were performed by WHAP. The rs3770748 within the QPCT gene showed a significant association with spine BMD in both single-marker (P = 0.002) and haplotype association analyses (P = 0.0482 for the global test; P = 0.00092 for the haplotype-specific test). Subgroup analysis revealed that the effect was primarily driven by an association in the postmenopausal women, presumably suggesting that the rs3770748 affects postmenopausal bone loss rather than peak bone mass. Our results suggest that QPCT may be the QTL gene at chromosome 2p for spine BMD variation in the Chinese population.