[A clinical study of Proteus syndrome caused by a mosaic somatic mutation in AKT1 gene].

Objective: Proteus syndrome is a rare disease. The aim of the present study was to analyze the clinical characteristics and gene mutations of Proteus syndrome with a case report and relevant literature review. Methods: Clinical data of the patient with Proteus syndrome were collected in detail and biochemical measurements and radiological examinations were conducted. Tissues from phalanges with lesions were obtained to extract DNA, and Sanger sequencing of AKT1 gene was carried on. The pathogenic mutation was further tested in peripheral blood samples of the patient, his parents and 250 healthy volunteers. Orthopaedic surgery was performed on the affected limbs of the patient. Results: The patient was presented with progressive overgrowth of the right extremity, scoliosis, cerebral connective tissue nevus and lower extremity venous. A heterozygous mutation of AKT1 gene (c. 49G>A) was identified in DNA extracted from the affected bone tissue of the patient, but not be found in genomic DNA of peripheral blood samples from the patient, his parents and 250 healthy volunteers. Movement function of the affected limb improved significantly after the operations. Conclusions: The prominent features of Proteus syndrome are overgrowth of one extremity and cerebral connective tissue nevus. A mosaic somatic mutation of AKT1 gene is one of the pathogenic mutations for Proteus syndrome, and orthopedic surgery may be a good way to improve symptoms of the disease.

Association between SOST gene polymorphisms and response to alendronate treatment in postmenopausal Chinese women with low bone mineral density.

The aim of this study was to explore the allelic association between SOST polymorphisms and the variance of clinical effects of alendronate in postmenopausal Chinese women with osteoporosis or osteopenia. In the study, 500 postmenopausal women in Shanghai area with osteoporosis or osteopenia were included. All participants were treated with weekly oral alendronate 70 mg, daily calcium 600 mg and vitamin D 125 IU for 12 months. Nine tagging single-nucleotide polymorphisms (SNPs) in SOST gene were genotyped. Bone mineral density of lumbar spine (L1-L4), left femoral neck and total hip were measured at baseline and after 1 year of treatment, respectively. In the study, 450 subjects completed the 1-year follow-up. The rs865429 was significantly associated with the % change of BMD at the femoral neck (P = 0.007). GG carriers seemed to be at an advantage after treatment of alendronate. Compared with AG and AA heterozygote, GG homozygote had the highest % change of BMD (3.100 ± 2.899%) at femoral neck. The odds ratio (95% confidence) of GG homozygote to be responders at femoral neck was 1.921 (1.211-3.048). Two haplotypes GG and AC constituted by rs865429 and rs851057 were associated with the % change of BMD at femoral neck and total hip, respectively. Therefore, the common variation of SOST gene contribute to the therapeutic response to alendronate treatment in Chinese women with osteoporosis or osteopenia.

The levels of bone turnover markers 25(OH)D and PTH and their relationship with bone mineral density in postmenopausal women in a suburban district in China.

This study evaluated the levels of bone turnover markers (BTMs) and investigated relationships between them and bone mineral density (BMD) in postmenopausal women in China suburban district. The prevalence of osteoporosis was 25.03 % at lumbar spine and 6.23 % at femoral neck, and BTMs were negatively correlated with BMDs. INTRODUCTION: The aims of this study were to evaluate the levels of bone turnover markers (BTMs), including serum N-terminal procollagen of type I collagen (P1NP), beta C-terminal cross-linked of type I collagen (ß-CTX), 25-hydroxyvitamin D [25(OH)D], and parathyroid hormone (PTH), and to investigate relationships between these markers and bone mineral density (BMD) as well the prevalence of osteoporosis in postmenopausal women of suburban district. METHODS: A population of 4822 postmenopausal women aged 55-69 years old (62.22 ± 6.75) from the suburban district was recruited voluntarily. BMD was measured at the lumbar spine, femoral neck, and total hip using dual-energy X-ray absorptiometry; 2251 women in this group had the serum BTMs 25(OH)D and PTH tested. RESULTS: The prevalence of osteoporosis was 25.03 % at lumbar spine and 6.23 % at femoral neck. The median (interquartile range) values of serum P1NP, ß-CTX, 25(OH)D, and PTH were 59.3 ng/mL (44.7-75.52), 0.370 ng/mL (0.280-0.490), 23.0 ng/mL (17.1-30.5), and 31.4 pg/mL (24.9-39.7), respectively. Serum P1NP and ß-CTX levels presented significantly negative correlations with BMDs at the all the sites (Betastd = -0.098 to -0.208, respectively, P < 0.001), whereas PTH levels were negatively correlated with BMDs of the femoral neck and total hip (Betastd = -0.062 and -0.054, P < 0.01, respectively). Serum 25(OH)D had positive associations with BMDs at total hip (Betastd = 0.051, P < 0.01). CONCLUSIONS: The BMD of postmenopausal women in China suburban area is higher than that in downtown area, and over 60 % of the participants had their serum 25(OH)D level over 20 ng/mL. BTMs were negatively correlated with BMDs, suggesting that BTMs are reliable factors for early declines in BMD.

Polymorphisms in Wnt signaling pathway genes are associated with peak bone mineral density, lean mass, and fat mass in Chinese male nuclear families.

UNLABELLED: Our objective was to investigate the associations between polymorphisms in Wnt pathway genes and peak bone mineral density (BMD) and body composition in young Chinese men. Our study identified that WNT5B and CTNNBL1 for both BMD and body composition, and WNT4 and CTNNB1 gene polymorphisms contribute to the variation in BMD and body composition in young Chinese men, respectively. INTRODUCTION: Our objective was to investigate the associations between polymorphisms in WNT4, WNT5B, WNT10B, WNT16, CTNNB1, and CTNNBL1 genes and peak bone mineral density (BMD), lean mass (LM), and fat mass (FM) in young Chinese men. METHODS: Using SNPscan(TM) kits, 51 single-nucleotide polymorphisms (SNPs) located in the 6 genes were genotyped in a total of 1214 subjects from 399 Chinese nuclear families. BMD, total lean mass (TLM), and total fat mass (TFM) were measured using dual energy X-ray absorptiometry (DXA). The associations between the 51 SNPs and peak BMD and body composition [including the TLM, percentage lean mass (PLM), TFM, percentage fat mass (PFM), and the body mass index (BMI)] were analyzed through quantitative transmission disequilibrium tests (QTDTs). RESULTS: For peak BMD, we found significant within-family associations of rs2240506, rs7308793, and rs4765830 in the WNT5B gene and rs10917157 in the WNT4 gene with the lumbar spine BMD (all P < 0.05). We detected an association of rs11830202, rs3809269, rs1029628, and rs6489301 in the WNT5B gene and rs2293303 in the CTNNB1 gene with body composition (all P < 0.05). For the CTNNBL1 gene, six SNPs (rs6126098, rs6091103, rs238303, rs6067647, rs8126174, and rs4811144) were associated with peak BMD of the lumbar spine, femoral neck, or total hip (all P < 0.05). Furthermore, two of the six SNPs (rs8126174 and rs4811144) were associated with body composition. CONCLUSIONS: This study identified WNT5B and CTNNBL1 for peak BMD and body composition in males from the Han Chinese ethnic group, and the results suggest a site-specific gene regulation. The WNT4 and CTNNB1 gene polymorphisms contribute to the variation in peak BMD and body composition, respectively.

Genetic polymorphisms in the mevalonate pathway affect the therapeutic response to alendronate treatment in postmenopausal Chinese women with low bone mineral density.

Alendronate is an antiosteoporotic drug that targets the mevalonate pathway. To investigate whether the genetic variations in this pathway affect the clinical efficacy of alendronate in postmenopausal Chinese women with osteopenia or osteoporosis, 23 single-nucleotide polymorphisms (SNPs) in 7 genes were genotyped in 500 patients treated with alendronate for 12 months. Bone mineral density (BMD) was measured at baseline and after 12 months. The rs10161126 SNP in the 3' flanking region of MVK and the GTCCA haplotype in FDFT1 were significantly associated with therapeutic response. A 6.6% increase in BMD in the lumbar spine was observed in the GG homozygotes of rs10161126; AG heterozygotes and AA homozygotes experienced a 4.4 and 4.5% increase, respectively. The odds ratio (95% confidence interval) of G allele carriers to be responders in lumbar spine BMD was 2.06 (1.08-6.41). GTCCA haplotype in FDFT1 was more frequently detected in the group of responders than in the group of non-responders at the total hip (2.6 vs 0.5%, P=0.009). Therefore, MVK and FDFT1 polymorphisms are genetic determinants for BMD response to alendronate therapy in postmenopausal Chinese women.

Associations of polymorphisms in the SOST gene and bone mineral density in postmenopausal Chinese Women.

UNLABELLED: The bone mineral density (BMD) of a total of 1,379 healthy postmenopausal Chinese women was measured. Ten tagging SNPs of the sclerostin (SOST) gene were genotyped. Our results suggest that the polymorphisms of the rs2023794 and rs74252774 in the SOST gene were associated with BMD of the lumbar spine in postmenopausal Chinese women. INTRODUCTION: The purpose of the study was to determine the associations between polymorphisms of SOST gene and BMD in postmenopausal Chinese women. METHODS: A total of 1,379 independent healthy postmenopausal Chinese women including 703 in our previous study were recruited. The BMD of the lumbar spine 1-4 (L1-4) and left proximal femur including total hip and femoral neck were measured by dual-energy X-ray absorptiometry. Ten tagging SNPs (rs1234612, rs1513670, rs1634330, rs1708635, rs2023794, rs7220711, rs74252774, rs851057, rs851058, and rs865429) of the SOST gene were genotyped. RESULTS: The rs2023794 and rs74252774 and the haplotype ACCATTCT of SOST gene were associated with age and body mass index (BMI) adjusted L1-4 BMD (P values were 0.010, 0.007, and 0.007, respectively) even after performing the Bonferroni multiple-significance-test correction. There was a clear trend in these regions that the CC genotype of the rs2023794 and the TT genotype of the rs74252774 have higher BMD values than other genotypes. The contributions of the rs2023794 and rs74252774 to the phenotypic variation of L1-4 BMD were 0.6 and 0.7 %, respectively. We failed to find any association between the 10 SNPs and 6 haplotypes of the SOST gene and BMD at the hip site in this study. CONCLUSIONS: Our results suggest that the polymorphisms of the rs2023794 and rs74252774 in the SOST gene were associated with BMD of the lumbar spine in a large sample of postmenopausal Chinese women.

Polymorphisms in the human ALOX12 and ALOX15 genes are associated with peak bone mineral density in Chinese nuclear families.

SUMMARY: Association between ten single-nucleotide polymorphisms (SNPs) in the human ALOX12 and ALOX15 genes and variations in peak bone mineral density (BMD) in a large sample of Chinese nuclear families with female offspring using the quantitative transmission disequilibrium test (QTDT). Our results suggest that the genetic polymorphisms in both human ALOX12 and ALOX15 may contribute to variations in the peak BMD of Chinese women. INTRODUCTION: The aim of this study was to investigate whether polymorphisms in the human ALOX12 and ALOX15 genes are associated with variations in peak BMD in Chinese nuclear families with female offspring. METHODS: Each five SNPs in the ALOX12 and ALOX15 genes were genotyped in a total of 1,260 individuals from 401 Chinese nuclear families. The BMD of the lumbar spine, femoral neck and total hip was measured by dual-energy X-ray absorptiometry. We tested whether a single SNP or a haplotype was associated with peak BMD variations using the QTDT. RESULTS: Using QTDT to measure within-family associations in ALOX15, we observed a significant association between rs916055 and BMD in the lumbar spine (p = 0.027 in the permutation 1,000 test). However, in ALOX12, rs312470 was significantly associated with BMD in the femoral neck (p = 0.029 and p = 0.036 in the permutation 1,000 test). The results of a haplotype analysis supported the findings of the single locus test for ALOX15. CONCLUSIONS: Our results suggest that the genetic polymorphisms in both human ALOX12 and ALOX15 may contribute to variations in the peak BMD of Chinese women.

ALOX12 polymorphisms are associated with fat mass but not peak bone mineral density in Chinese nuclear families.

OBJECTIVE: Arachidonate 12-lipoxygenase (ALOX12) is a member of the lipoxygenase superfamily, which catalyzes the incorporation of molecular oxygen into polyunsaturated fatty acids. The products of ALOX12 reactions serve as endogenous ligands for peroxisome proliferator-activated receptor γ (PPARG). The activation of the PPARG pathway in marrow-derived mesenchymal progenitors stimulates adipogenesis and inhibits osteoblastogenesis. Our objective was to determine whether polymorphisms in the ALOX12 gene were associated with variations in peak bone mineral density (BMD) and obesity phenotypes in young Chinese men. METHODS: All six tagging single-nucleotide polymorphisms (SNPs) in the ALOX12 gene were genotyped in a total of 1215 subjects from 400 Chinese nuclear families by allele-specific polymerase chain reaction. The BMD at the lumbar spine and hip, total fat mass (TFM) and total lean mass (TLM) were measured using dual-energy X-ray absorptiometry. The pairwise linkage disequilibrium among SNPs was measured, and the haplotype blocks were inferred. Both the individual SNP markers and the haplotypes were tested for an association with the peak BMD, body mass index, TFM, TLM and percentage fat mass (PFM) using the quantitative transmission disequilibrium test (QTDT). RESULTS: Using the QTDT, significant within-family association was found between the rs2073438 polymorphism in the ALOX12 gene and the TFM and PFM (P=0.007 and 0.012, respectively). Haplotype analyses were combined with our individual SNP results and remained significant even after correction for multiple testing. However, we failed to find significant within-family associations between ALOX12 SNPs and the BMD at any bone site in young Chinese men. CONCLUSIONS: Our present results suggest that the rs2073438 polymorphism of ALOX12 contributes to the variation of obesity phenotypes in young Chinese men, although we failed to replicate the association with the peak BMD variation in this sample. Further independent studies are needed to confirm our findings.

[Investigation on genotype constitution of different Plasmodium vivax isolates and its geographical distribution in China].

OBJECTIVE: To investigate the population constitution and geographical distribution of Plasmodium vivax in China using molecular technique. METHODS: Blood-spot filter paper samples with related epidemiological data were collected from vivax malaria patients living in malarious area of 10 provinces (autonomous region) in China. Semi-nested- or nested-allelic-specific PCR genotyping method was used to identify CSP genotypes, families and types of Plasmodium vivax of each isolate from these patients. RESULTS: Of 384 field isolates of Plasmodium vivax, 258 temperate zone family strains were identified, including 14 allelic variant genotypes spreading among 10 sampling provinces; allelic variants sized less than 731 bp were only seen in 5 provinces in southern China; 79 tropical zone family strains including 5 genotypes were also distributed in 5 provinces of southern China south to 25 degrees N. lat; and 14 PV Type-2 strains including 2 genotypes were found in some areas of Hainan and Yunnan Provinces. In addition, 33 isolates from genotype-mixed infections were revealed. CONCLUSION: At present, area north to 25 degrees N. lat. of the country is the sole area prevalent for Plasmodium vivax family strains of temperate zone; there is overlapping distribution of P. v. of temperate zone family and tropical zone family of this parasite in the southern China south to 25 degrees N. lat; where the most complex isolate constitution is in Yunnan and Hainan Provinces, and PV Type-2 strains have been found in some areas of the two provinces. Besides, there were 2 groups of genotype with distinct geographic distribution feature within the temperate zone family.

[Studies on identification of circumsporozoite protein genotyping of Plasmodium vivax].

OBJECTIVE: To develop a new method of genotyping circumsporozoite protein (CSP) gene for identification of field isolates of Plasmodium vivax. METHODS: Improved Chelex-100 ion-exchange method was used to extract DNA from blood filter paper samples, nested PCR and allele-specific PCR techniques, agarose gel electrophoresis analysis and dot/southern blotting-probe hybridization were employed for amplification, resolution and identification of the diagnostic fragments. RESULTS: Using the nest-allele-specific PCR assay reported here, small amounts of DNA extracted from a piece of blood filter paper sample were amplified which produced three different size ranges of diagnostic bands: 650-770 bp PV-species-specific band, 170-230 bp diagnostic band for temperate zone family and 588 bp band for PV type-2. The sizes and patterns of the bands produced by the reference strains were consistent with those of designed target sequences. Of 59 examined isolates from 6 provinces of China, 42 temperate zone family strains, 15 tropical zone family strains and two PV type-2 strains were identified. CONCLUSION: 1, Three genotype strains of P. vivax mentioned above could be identified by this method with only two rounds of PCR and without probe hybridization. 2, The preliminary results showed that PV type-1 including temperate zone family strains and tropical zone family strains as well as PV type-2 strains are present in China. In addition, another CSP genotype with both sequence characteristics of temperate zone and tropical zone family might also be present in China.

[Environmental pollution, human exposure and its health effect of sodium pentachlorophenate in schistosomiasis prevalent area].

Sodium pentachlorophenate (Na-PCP) has been used in China for years as an molluscacide to kill oncomelania, which is an intermediate host of Schistosome. To evaluate the effects of its long-term successive usage on environment, human exposure and health, studies were carried out in Sichuan, Jiangxi, Jiangsu and Fujian provinces, with a time gap of more than one month between sample collection and last spray of Na-PCP. Results indicated that PCP contents in surface water, soil, sediment, animals and plants were significantly higher in studied areas than in control areas. The daily intake and the content in urine of PCP were also sigificantify higher in studied areas. But, there was no difference on physical and biochemical examinations except that a 22%-28% decrease of blood cholinesterase activity was found in studied areas. The health effect of impurities in Na-PCP, dioxins and furans, was assessed and discussed.

[Effects of mercury exposure on reproduction in female workers].

Reproductive hazards in 704 female workers exposed to low-level metallic mercury and 583 controls were investigated. Females exposed to low-level mercury for a long term mainly manifested dysmenorrhoea, and the incidence of dysmenorrhoea increased with exposure dose, suggesting a dose-response relationship. At a level over 0.06 mg/m3 of mercury, incidence of hypomenorrhea significantly increased, and in general, at a level below 0.06 mg/m3, menstrual cycles, quantity and duration of menstrual flow did not change significantly. Differences in incidences of preterm delivery, spontaneous abortion, fetal death, still birth, and complications of pregnancy between the group exposed to 0.06-0.1 mg/m3 of mercury and the control group did not reach a significant level. Incidences of birth defect, neonatal asphyxia, neonatal death, infant infection, low birth weight, retardation on physical and mental development in offsprings of the exposed females were not significantly higher than in those of controls.