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Zheng X Ren W Zhang S Liu J Li S Li J Yang P He J Su S Li P 《Molecular biology reports》2012,39(1):17-23
TCF7L2 and SLC30A8 have been found to be associated with type 2 diabetes mellitus (T2DM) as well as with impaired proinsulin
processing recently, enzymes encoded by PCSK1 and PCSK2 are reported to play an important role in the process of proinsulin
conversion. To investigate whether the single nucleotide polymorphisms (SNPs) of TCF7L2, SLC30A8, PCSK1 and PCSK2 were associated
with T2DM as well as with proinsulin conversion in a Han Chinese population from Chongqing. A case–control study was performed
in Han Chinese subjects with normal control (n = 152) and T2DM (n = 227), we genotyped rs7903146 and rs11196218 at TCF7L2, rs13266634 at SLC30A8, rs3811951 at PCSK1 and rs2021785 at PCSK2.
Plasma levels of proinsulin were measured with an Enzyme Linked Immunosorbent Assay (ELISA). Genotype distribution and associations
with T2DM and fasting levels of proinsulin and proinsulin/insulin ratios were analyzed. We confirmed the association of risk
allele of rs2021785 at PCSK2 with type 2 diabetes also existed in Han Chinese population [OR = 1.4489 with 95% CI (1.0285,
2.0412), P = 0.0335]. Rs13266634 at SLC30A8 had a tendency to be associated with fasting plasma levels of proinsulin (P = 0.0639 in additive model). We did not find the significant association between other SNPs and T2DM or fasting levels of
proinsulin or proinsulin/insulin ratios. Our results provide evidence that the association of PCSK2 and T2DM was also existed
in Han Chinese population in Chongqing. We were underpowered to detect the association between other SNPs and T2DM or proinsulin
conversion. 相似文献
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Guinan KJ 《Biochemical genetics》2012,50(3-4):159-179
Type II diabetes is a multifactorial disease with a complex etiology. Numerous genes have been implicated in disease pathogenesis. In particular, SNPs at the TCF7L2 locus have consistently shown strong associations with type II diabetes. This study characterizes the global distribution of type II diabetes-associated TCF7L2 SNPs utilizing HapMap, HGDP-CEPH, and Alfred databases and the literature. High frequencies of rs7903146(T), rs12255372(T), and rs7901695(C) SNPs are observed in Africa, Europe, and the Middle East, but they are reduced and almost absent in Southeast Asian and Native American populations. In contrast, rs11196218(A) has the highest frequency in Eurasia but is reduced in sub-Saharan African and Native American populations. Regional variations in rs7903146(T) follow a gradient of decreasing frequency from southern into northeastern Europe. These findings demonstrate extensive global and regional variations in the frequencies of TCF7L2 SNPs, which may contribute to differences in the incidence of type II diabetes worldwide. 相似文献
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Shafat Ali Rupali Chopra Siddharth Manvati Yoginder Pal Singh Nabodita Kaul Anita Behura Ankit Mahajan Prabodh Sehajpal Subash Gupta Manoj K. Dhar Gagan B. N. Chainy Amarjit S. Bhanwer Swarkar Sharma Rameshwar N. K. Bamezai 《PloS one》2013,8(3)
Type 2 diabetes (T2D) is a syndrome of multiple metabolic disorders and is genetically heterogeneous. India comprises one of the largest global populations with highest number of reported type 2 diabetes cases. However, limited information about T2D associated loci is available for Indian populations. It is, therefore, pertinent to evaluate the previously associated candidates as well as identify novel genetic variations in Indian populations to understand the extent of genetic heterogeneity. We chose to do a cost effective high-throughput mass-array genotyping and studied the candidate gene variations associated with T2D in literature. In this case-control candidate genes association study, 91 SNPs from 55 candidate genes have been analyzed in three geographically independent population groups from India. We report the genetic variants in five candidate genes: TCF7L2, HHEX, ENPP1, IDE and FTO, are significantly associated (after Bonferroni correction, p<5.5E−04) with T2D susceptibility in combined population. Interestingly, SNP rs7903146 of the TCF7L2 gene passed the genome wide significance threshold (combined P value = 2.05E−08) in the studied populations. We also observed the association of rs7903146 with blood glucose (fasting and postprandial) levels, supporting the role of TCF7L2 gene in blood glucose homeostasis. Further, we noted that the moderate risk provided by the independently associated loci in combined population with Odds Ratio (OR)<1.38 increased to OR = 2.44, (95%CI = 1.67–3.59) when the risk providing genotypes of TCF7L2, HHEX, ENPP1 and FTO genes were combined, suggesting the importance of gene-gene interactions evaluation in complex disorders like T2D. 相似文献
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Nasser M. Al-Daghri Khalid M. Alkharfy Omar S. Al-Attas Soundararajan Krishnaswamy Abdul Khader Mohammed Omar M. Albagha Amal M. Alenad George P. Chrousos Majed S. Alokail 《Molecular biology reports》2014,41(3):1731-1740
Obesity, commonly measured as body mass index (BMI), has been on a rapid rise around the world and is an underlying cause of several chronic non-communicable diseases, including type 2 diabetes mellitus (T2DM). In addition to the environmental factors, genetic factors may also contribute to the ongoing obesity epidemic in Saudi Arabia. This study investigated the association between variants of 36 previously established T2DM SNPs and obesity phenotypes in a population of Saudi subjects. Study subjects consisted of 975 obese (BMI: ≥30), 825 overweight (25–30) and 423 lean controls (18–25) and of these 927 had a history of T2DM. Subjects were genotyped for 36 SNPs, which have been previously proved to be T2DM linked, using the KASPar method and the means of BMI and waist circumference (WC) corresponding to each of the genotypes were compared by additive, recessive and dominant genetic models. Five and seven of 36 T2DM-related SNPs were significantly associated with the BMI and WC, respectively. Variants of SNPs rs7903146, rs1552224 and rs11642841 in the control group and rs7903146 in T2DM group showed significant association with both BMI and WC. Variant of SNP rs10440833 was significantly associated with BMI in T2DM group of both males [OR = 1.8 (1.0, 3.3); P = 0.04] and females [OR = 2.0 (1.0, 3.9); P = 0.04]. Genetic risk scores explained 19 and 14 % of WC and hip size variance in this population. Variants of a number of established T2DM related SNPs were associated with obesity phenotypes and may be significant hereditary factors in the pathogenesis of T2DM. 相似文献
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