Comprehensive screening for reg1α gene rules out association with tropical calcific pancreatitis

AIM: To investigate the allelic and haplotypic association of reg1α gene with tropical calcific pancreatitis (TCP). Since TCP is known to have a variable genetic basis, we investigated the interaction between mutations in the susceptibility genes, SPINK1 and CTSB with reg1α polymorphisms. METHODS: We analyzed the polymorphisms in the reg1α gene by sequencing the gene including its promoter region in 195 TCP patients and 150 ethnically matched controls, compared their allele and haplotype frequencies, and their association with the pathogenesis and pancreaticolithiasis in TCP and fibro-calculous pancreatic diabetes. RESULTS: We found 8 reported and 2 novel polymo-rphisms including an insertion-deletion polymorphism in the promoter region of reg1α. None of the 5' UTR variants altered any known transcription factor binding sites, neither did any show a statistically significant association with TCP. No association with any reg1α variants was observed on dichotomization of patients based on their N34S SPINK1 or L26V CTSB status. CONCLUSION: Polymorphisms in reg1α gene, including the regulatory variants singly or in combination with the known mutations in SPINK1 and/or CTSB genes, are not associated with tropical calcific pancreatitis.

氘、氚代聚苯乙烯单体abinitio研究

用HF ,MP2 及BLYP从头算方法 ,在 6— 31G 基组水平上 ,优化了聚苯乙烯单体基态的平衡几何构型 .主要用BLYP 6— 31 方法研究了氘、氚代聚苯乙烯单体 (DPS ,PST)的正则振动频率、红外光谱强度、C—D键键能 ,并对正则振动模式进行了简单分析 ,同时研究了DPS ,PST单体中温度、压强与熵的关系 .

No association between cyclooxygenase-2 and uridine diphosphate glucuronosyltransferase 1A6 genetic polymorphisms and colon cancer risk

AIM：To investigate the association of variations in the cyclooxygenase-2 （COX2） and uridine diphosphate glucuronosyltransferase 1A6 （UGTIA6） genes and non-steroidal anti-inflammatory drugs （NSAIDs） use with risk of colon cancer.METHODS： NSAIDs, which are known to reduce the risk of colon cancer, act directly on COX2 and reduce its activity. Epidemiological studies have associated variations in the COX2 gene with colon cancer risk, but others were unable to replicate this finding. Similarly,enzymes in the UGT1A6 gene have been demonstrated to modify the therapeutic effect of NSAIDs on colon adenomas. Polymorphisms in the UGTIA6 gene have been statistically shown to interact with NSAID intake to influence risk of developing colon adenomas, but not colon cancer. Here we examined the association of tagging single nucleotide polymorphisms （SNPs） in the COX2 and UGTIA6 genes, and their interaction with NSAID consumption, on risk of colon cancer in a population of 422 colon cancer cases and 481 population controls.RESULTS： No SNP in either gene was individually statistically significantly associated with colon cancer, nor did they statistically significantly change the protective effect of NSAID consumption in our sample. Like others, we were unable to replicate the association of variants in the COX2 gene with colon cancer risk （P 〉 0.05）,and we did not observe that these variants modify the protective effect of NSAIDs （P 〉 0.05）. We were able to confirm the lack of association of variants in UGT1A6 with colon cancer risk, although further studies will have to be conducted to confirm the association of these variants with colon adenomas.CONCLUSION： Our study does not support a role of COX2 and UGTIA6 genetic variations in the development of colon cancer.

Bivariate genome-wide association study suggests that the DARC gene influences lean body mass and age at menarche

Lean body mass （LBM） and age at menarche （AAM） are two important complex traits for human health. The aim of this study was to identify pleiotropic genes for both traits using a powerful bivariate genome-wide association study （GWAS）. Two stud- ies, a discovery study and a replication study, were performed. In the discovery study, 909622 single nucleotide polymor- phisms （SNPs） were genotyped in 801 unrelated female Han Chinese subjects using the Affymetrix human genome-wide SNP array 6.0 platform. Then, a bivariate GWAS was performed to identify the SNPs that may be important for LBM and AAM. In the replication study, significant findings from the discovery study were validated in 1692 unrelated Caucasian female subjects One SNP rs3027009 that was bivafiately associated with left arm lean mass and AAM in the discovery samples （P=7.26x10-6） and in the replication samples （P=0.005） was identified. The SNP is located at the upstream of DARC （Duffy antigen receptor for chemokines） gene, suggesting that DARC may play an important role in regulating the metabolisms of both LBM and AAM.