Vascular endothelial growth factor polymorphisms and risk of Alzheimer's disease: A meta-analysis

There were conflicting results about whether promoter polymorphisms (− 2578C/A, − 1154G/A) of vascular endothelial growth factor (VEGF) gene is a risk factor of Alzheimer's disease (AD). To determine the relationship between them, a meta-analysis is needed urgently. We searched all the reports about VEGF promoter polymorphisms (− 2578C/A, − 1154G/A) and AD risk from PubMed, Web of Science, Cochrane Collaboration and Google Scholar database for the period up to 1 August, 2012. A total of 7 studies were included in this meta-analysis. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated applying fixed or random effects models. There was no significant association between VEGF − 2578C/A polymorphisms and AD risk in all gene models (OR = 1.08, 95% CI = 0.94–1.23 for A vs. C; OR = 1.19, 95% CI = 0.89–1.59 for AA vs. CC; OR = 1.15, 95% CI = 0.91–1.45 for AA vs. CC + CA; OR = 1.11, 95% CI = 0.98–1.25 for AA + CA vs. CC). Similar results were provided in subgroup analysis by ethnicity. For the VEGF − 1154G/A polymorphisms, lack of an association was also found (A vs. G: OR = 0.89, 95% CI = 0.79–1.01; AA vs. GG: OR = 0.82, 95% CI = 0.62–1.08; AA vs. GA + GG: OR = 0.89, 95% CI = 0.68–1.16; AA + AG vs. GG: OR = 0.85, 95% CI = 0.72–1.00). Conclusively, the result of this meta-analysis suggested that VEGF promoter polymorphisms (− 2578C/A, − 1154G/A) might not contribute to the susceptibility of AD.     

Gene polymorphism of vascular endothelial growth factor −1154 G>A is associated with hypertensive nephropathy in a Hispanic population

The aim of this study was to determine the association between hypertensive nephropathy and gene polymorphisms of vascular endothelial growth factor (VEGF) in a self-reported Hispanic patient group. A total of 155 Hispanic living kidney donors as controls and a total of 86 Hispanic kidney transplant patients, whose renal failure was attributed to hypertensive nephropathy after ruling out diabetes mellitus or other causes, were genotyped for four different single nucleotide polymorphisms of VEGF: −2578 C>A (rs699947), −1154 G>A (rs1570360), −460 C>T (rs833061), and +936 C>T (rs3025039). The homozygous mutant type (AA) of VEGF −1154 G>A (rs1570360) was found with significantly higher frequency in the hypertensive nephropathy patients than in controls. On the other hand, homozygous wild type (GG) was found less frequently in the hypertensive nephropathy patient group than in the control group. Linkage disequilibrium (LD) analyses revealed a high degree of LD among VEGF −2578 C>A (rs699947), VEGF −1154 G>A (rs1570360), and VEGF −460 C>T (rs833061). The haplotype analysis revealed that two haplotypes, CGTC and CATC (in the order of VEGF −2578 C>A (rs699947), −1154 G>A (1570360), −460 C>T (rs833061), and +936 C>T (3025039)), were significantly associated with hypertensive nephropathy in Hispanic patients. Hence, the −1154 G>A polymorphism (rs1570360) and two haplotypes (CGTC and CATC) of VEGF appear to be associated with hypertensive nephropathy in Hispanic patients who developed end-stage renal disease requiring kidney transplant.     

Vascular endothelial growth factor gene polymorphisms and colorectal cancer risk: a meta-analysis

Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen involved in a number of pathologic processes, including angiogenesis, tumor growth and metastasis. Polymorphisms of the VEGF gene have been associated with susceptibility to colorectal cancer (CRC). However, the specific association still remains controversial. We made a meta-analysis of the association between VEGF gene polymorphisms and CRC risk. Only eight case-control studies were retrieved, with a total of 2337 CRC patients and 2032 healthy controls. Six VEGF gene polymorphisms were addressed in all studies included, +936C>T (rs3025039), -2578C>A (rs699947), -1154G>A (rs1570360), -634G>C (rs2010963), -460C>T (rs833061), and +405C>G (rs2010963). There was a significant association between -2578C>A polymorphism and susceptibility to CRC in the comparison of C allele carriers (CC + CA) versus AA (odds ratio = 0.77, 95% confidence interval = 0.62-0.96, P = 0.02). No association was found between +936C>T, -1154G>A, -634G>C, -460C>T, and +405C>G with susceptibility to CRC. We conclude that the C allele carrier (CC + CA) of VEGF -2578C>A polymorphism appears to be a protective factor for CRC.     

Association of common variants of vascular endothelial growth factor and interleukin-18 genes with allograft survival in renal transplant recipients of North India

Increased vascular endothelial growth factor (VEGF) production promotes enhanced endothelial permeability, enhanced leukocyte migration into the allograft, thereby leading to a clinically recognized rejection episode. Interleukin-18 (IL-18), a potent proinflammatory cytokine, may also be involved in mechanisms of kidney allograft rejection. The present study was, therefore, undertaken to investigate the association of functional polymorphisms in VEGF (2578C>A, 1154A>G) and IL-18 (607C>A, 137G>C) genes with risk of allograft rejection in renal transplant recipients of North India. Two hundred renal transplant recipients, 150 matched recipients-donors, and 200 unrelated healthy individuals were genotyped by amplification refractory mutation specific polymerase chain reaction and by polymerase chain reaction-restriction fragment length polymorphism. Variant allele VEGF 1154A>G (p?=?0.56; odds ratio [OR]?=?1.32) and variant allele (p?=?0.004, OR?=?1.54) and variant genotype (p?=?0.007, OR?=?3.26) of IL-18 607C>A, GC of IL-18 137G>C (p?=?0.043, OR?=?0.63) were significantly different in healthy individuals as compared with the patients with renal transplant. When 114 nonrejectors were compared with 36 rejectors (150 recipients) for association with allograft rejection, significant association was observed in heterozygous genotype of VEGF 2578C>A (p?=?0.033), VEGF 1154A>G (p?=?0.024). In IL-18 137G>C, CC genotype, C allele showed protective association with allograft rejection. Kaplan-Meier analysis indicated a higher mean time for first rejection episode in CA genotype carriers (31 months) as compared with AA (29 months) for VEGF 2578C>A (log p?=?0.035). In VEGF, the haplotypes A-A and A-G (2578-1154) were associated with reduced risk and in IL-18 607A-137G, they were associated with high risk for allograft rejection. This observation suggests these polymorphisms are an ideal marker for prediction of pretransplant allograft outcome.     

Five polymorphisms of vascular endothelial growth factor (VEGF) and risk of breast cancer: a meta-analysis involving 16,703 individuals

Associations between five polymorphisms of vascular endothelial growth factor (i.e., VEGF +936C/T, −1154A/G, −2578C/A, −634G/C and −460T/C) and risk of breast cancer have been extensively studied, and the currently available results are inconclusive. Therefore, we performed this meta-analysis to further study the associations. The databases of Pubmed, Embase and CNKI were retrieved up to April 1st, 2010. The pooled ORs and 95% CIs were used to assess the strength of the associations. A total of 10 case–control studies with 8175 cases and 8528 controls were included in this study. The overall results of combined analyses showed that five polymorphisms of VEGF were not associated with risk of breast cancer [ORs (95% CIs): 1.03 (0.84–1.27) for CC vs. TT for +936C/T, 0.95 (0.81–1.12) for AA vs. GG for −1154A/G, 1.01 (0.90–1.14) for CC vs. AA for −2578C/A, 1.02 (0.90–1.16) for GG vs. CC for −634G/C and 0.86 (0.68–1.09) for TT vs. CC for −460T/C]. When subgroup analyses by ethnicity for VEGF +936C/T and −634G/C, the results suggested that +936C/T was not associated with the risk of breast cancer for either Asians [1.40 (0.92–2.13) for CC vs. TT and CC + CT vs. TT: 1.38 (0.91–2.10) for CC + CT vs. TT] or Caucasians [0.93 (0.73–1.19) for CC vs. TT and 0.91 (0.72–1.16) for CC + CT vs. TT], and −634G/C was not associated with the breast cancer for Caucasians [1.07 (0.92–1.24) for GG vs. CC and 1.05 (0.91–1.21) for GG + GC vs. CC]. In addition, when excluding one study, which was out of Hardy–Weinberg equilibrium for VEGF +963C/T and whose controls were from both patients and healthy people, the negative results were also persistent, and ORs (95% CIs) were 1.04 (0.84–1.29) for CC vs. TT, 1.03 (0.83–1.27) for (CC + CT) vs. TT. This meta-analysis suggests that the VEGF +936C/T, −1154A/G, −2578C/A, −634G/C and −460T/C may be not associated with risk of breast cancer development based on the currently available studies, especially for Caucasians. More well designed studies with larger sample size on different ethnicities are needed to further assess the associations.     

Genetic polymorphisms for vascular endothelial growth factor in perinatal complications

Low birth weight (LBW) infants have increased susceptibility to perinatal complications. An immature and impaired vascular system may possibly participate in these complications. There is evidence that supports the notion that vascular endothelial growth factor (VEGF), which is an essential regulator of embryonic angiogenesis, plays a central role in the pathogenesis of perinatal complications. We aimed to test whether functional genetic polymorphisms of VEGF are associated with the risk of preterm birth or perinatal morbidity. We enrolled 128 LBW infants (< or = 1500 grams). VEGF T-460C, VEGF C-2578A and VEGF G+405C polymorphisms were determined by real-time PCR or PCR-RFLP, respectively. Their genotypes were compared with VEGF genotypes of 200 healthy, term neonates. The prevalence of the VEGF+405 C allele was higher in LBW infants than in healthy, term neonates (OR [95% CI]: 1.29 [1.01-1.65]). Carrier state for the VEGF -2578A allele was an independent risk factor for enterocolitis necrotisans (NEC) (adjusted OR [95% CI]: 2.77 [1.00-7.65]). The carrier state for the VEGF -2578AA genotype was associated with a decreased risk of acute renal failure (ARF) (adjusted OR [95% CI]: 0.2 [0.05-0.78]). These results suggest that VEGF G+405C polymorphism might be associated with a higher risk of preterm birth and that VEGF C-2578A polymorphism may participate in the development of perinatal complications such as NEC and ARF.     

DNA sequence variation in the promoter region of the VEGF gene impacts VEGF gene expression and maximal oxygen consumption

In its role as an endothelial cell proliferation and migration factor, vascular endothelial growth factor (VEGF) can affect peripheral circulation and therefore impact maximal oxygen consumption (Vo2 max). Because of the role of VEGF, and because variation in the VEGF gene has the ability to alter VEGF gene expression and VEGF protein level, we hypothesized that VEGF gene polymorphisms are related to VEGF gene expression in human myoblasts and Vo2 max before and after aerobic exercise training. We analyzed the effects of the VEGF -2578/-1154/-634 promoter region haplotype on VEGF gene expression by using a luciferase reporter assay in cultured human myoblasts and found that the AAG and CGC haplotypes resulted in significantly higher hypoxia-stimulated VEGF gene expression than the AGG and CGG haplotypes. Consistent with these results, we found that individuals with at least one copy of the AAG or CGC haplotype had higher Vo2 max before and after aerobic exercise training than did subjects with only the AGG and/or CGG haplotype. In conclusion, we found that VEGF -2578/-1154/-634 haplotype impacts VEGF gene expression in human myoblasts and is associated with Vo2 max. These results have potential implications for aerobic exercise training and may prove relevant in the study of pathological conditions that can be affected by angiogenesis, such as coronary artery disease and peripheral artery disease.     

Association of vascular endothelial growth factor gene polymorphisms with osteoporotic vertebral compression fractures in postmenopausal women

Vascular endothelial growth factor (VEGF) is involved in bone formation through its role in angiogenesis. VEGF is also known to promote the healing of fractures. Thus, we determined whether or not VEGF ?2578C>A, ?1154G>A, ?634G>C, and 936C>T polymorphisms and haplotypes are associated with osteoporotic vertebral compression fractures (OVCF) in postmenopausal Korean women. The study subjects consisted of 82 patients with osteoporotic vertebral compression fractures and 117 control postmenopausal Korean women. PCR-RFLP and real-time PCR were used to analyze the VEGF polymorphisms. Homocysteine levels were also measured to determine whether or not polymorphisms of the VEGFgene affect homocysteine/folate metabolism. The AA genotype of the ?2578C>A polymorphism was significantly different between the stroke and control groups; no significant differences in the ?1154G>A, ?634G>C, and 936C>T genotype frequencies existed. However, the A-G-G-C haplotype had a tendency to be associated with OVCF in postmenopausal Korean women. Associations between the VEGF ?2578C>A polymorphism and homocysteine levels were also noted. In summary, these results suggest that the VEGF ?2578C>A polymorphisms and VEGF haplotypes may play an important role in the etiology of OVCF in postmenopausal Korean women.     

Association of VEGF genetic polymorphisms with prostate carcinoma risk and clinical outcome

OBJECTIVES: Vascular endothelial growth factor (VEGF) is a potent stimulus of angiogenesis that has an important role in many human malignancies including prostate carcinoma (PCa). We evaluated the role of the functional VEGF polymorphisms as genetic markers for PCa susceptibility and prognosis. METHODS: The study included 101 patients with PCa and [corrected] 100 age-matched healthy men. The VEGF genotypes -1154G>A were identified by allele-specific polymerase chain reaction (AS-PCR) and the genotypes -634G>C and 936C>T were identified by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR). RESULTS: A negative association was found between VEGF -1154AA genotype and PCa risk (OR=0.27; P=0.009). Furthermore, the presence of the VEGF -1154A allele appeared to be associated with a decreased [corrected] risk of higher tumor grade (OR=0.37; P=0.01). A significant increased risk of prostate cancer was associated with the VEGF -634 (GC+CC) combined genotype (OR=1.95; P=0.02). The VEGF -634C allele was associated with the aggressive phenotype of prostate cancer as defined by the high histological grade (OR=3.48; P=0.007). The VEGF -1154A/-634G haplotype was negatively associated with PCa risk (OR=0.48; P=0.005) and high tumor grade compared to low grade (OR=0.37; P=0.02). CONCLUSIONS: Genetic variations in the VEGF may predict not only PCa risk but also tumor aggressiveness.     

Correlation of VEGF genetic polymorphisms and lipid profile to aortic calcification

Background

Aortic calcification is developed due to accumulation of a large amount of calcium in the aorta of the heart and it is the leading cause of aortic valve replacement and third leading cause of cardiovascular disease. The purpose of this study was to investigate the relation between aortic calcification and VEGF SNPs (− 2578C>A, − 1154G>A and + 936C>T) and to evaluate the association of these SNPs with biochemical parameter in relation to aortic calcification.

Methods

Aortic calcification was diagnosed by examining the posteroanterior chest X-rays by a radiologist and graded into four groups. The real-time polymerase chain reaction with melting curve analysis in LightCycler was used to genotype the VEGF SNPs.

Results

Among the VEGF SNPs, a significant genetic difference was found only between the aortic calcification and control group with VEGF SNP − 2578C>A but haplotypes T–A–A of (+ 936/− 1154/− 2578) were significantly different in control and aortic calcification and could enhance the aortic calcification development. By regression analysis, it was found that age, hypertension, diabetes, dyslipidemia, and hyperhomocysteinemia were found significantly different with the different genotypes of VEGF SNPs which may induce aortic calcification development.

Conclusion

Age, hypertension, diabetes, dyslipidemia, and hyperhomocysteinemia were established as aggravating factors for the aortic calcification in association with different VEGF genotypes.     

Polymorphism of vascular endothelial growth factor −1154G>A (rs1570360) with cancer risk: a meta-analysis of 16 case–control studies

Published data on the association of vascular endothelial growth factor (VEGF) −1154G>A polymorphism with cancer risk is inconclusive. To derive a more precise estimation of association between VEGF −1154G>A polymorphism and the risk of cancer, we performed a meta-analysis of 7,071 cancer cases and 7,693 controls from 16 published case–control studies. Our meta-analysis didn’t reveal an association between VEGF −1154G>A polymorphism and overall cancer risk (GG vs. AA: OR: 1.08, 95% CI: 0.96–1.20; GA vs. AA: OR: 1.04, 95% CI: 0.93–1.17; recessive model: GG+GA vs. AA: OR: 1.06, 95% CI: 0.95–1.18; dominant model: GG vs. GA+AA, OR: 1.11, 95% CI: 1.00–1.24). Nevertheless, for non-Caucasians, GG homozygote may have higher cancer risk compared with either A carriers (OR: 1.58, 95% CI: 1.12–2.23) or AA homozygote (OR: 1.43, 95% CI: 1.17–1.76). No significant heterogeneity was detected except in the dominant model and “prostate cancer” subgroup analysis. More studies with larger samples are warranted to confirm these findings.     

Novel polymorphisms of goat growth hormone and growth hormone receptor genes and their effects on growth traits

In this study, the polymorphisms of growth hormone (GH) gene 5' promoter region and intron 8, exons 4 and 10 of growth hormone receptor (GHR) gene were analyzed in Xinong Saanen goats (SG) and Boer goats (BG). Two alleles (A and B) and three genotypes (AA, AB and BB) were detected at P1 locus of GH gene, and two alleles (G and T) and two genotypes (GG and GT) were detected at P4 locus of GHR gene by PCR-SSCP analysis. In addition, two single nucleotide polymorphisms (SNPs)-A73C (P1 locus) and G114T (P4 locus), were identified by DNA sequencing. The frequencies of alleles A and B in the two goat breeds were 0.61-0.62, and 0.39-0.38, respectively, and the frequencies of alleles G and T in the two goat breeds were 0.82-0.86, and 0.18-0.14, respectively. The SNP loci were in Hardy-Weinberg disequilibrium in both goat breeds (P<0.05). Polymorphisms of GH and GHR genes were shown to be associated with growth traits in BG breed. AA and GG genotypes were associated with superior growth traits in 1-, 2- and 3-month old individuals. Hence, AA and GG genotypes are suggested to be a molecular marker for superior growth traits in BG breed.     

Meta-analysis of MCP-1 promoter ?2518 A/G polymorphism and SLE susceptibility

The aim of this meta-analysis was to summarize results on the association of monocyte chemoattractant protein-1(MCP-1) promoter -2518 A/G polymorphism with systemic lupus erythematosus (SLE) susceptibility. We searches all the publications about the association between MCP-1 promoter -2518 A/G polymorphism and SLE from Pubmed, Elsevier Science Direct, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure. The meta-analysis was performed for genotypes AA verse GG, AA+AG verse GG, AA verse AG+GG, and A allele verse G allele in a fixed/random effect model. A total of 14 studies (2,333 cases and 2,391 controls) were included in the meta-analysis. When all groups were pooled, we had not observed significant association between A allele and G allele (OR = 0.94, 95 %CI = 0.79-1.12, P = 0.50). When analysis were restricted to more ethnically homogeneous populations, the similar results were found in European population and Asian population (OR = 1.05, 95 %CI = 0.75-1.46, P = 0.80; OR = 1.00, 95 %CI = 0.86-1.17, P = 0.99). However, we had not detected a significant association between MCP-1 promoter -2518 A/G polymorphism and SLE when examining the genotypes AA verse GG, AA+AG verse GG, AA verse AG+GG. The meta-analysis did not demonstrate the association between MCP-1 promoter -2518 A/G polymorphism and SLE.     

Vascular endothelial growth factor and recurrent spontaneous abortion: A meta-analysis

To evaluate the association between vascular endothelial growth factor (VEGF) gene polymorphisms and the risk of recurrent spontaneous abortion (RSA), a meta-analysis of published case–control studies for the VEGF gene polymorphisms (gene polymorphisms reported more than three times were selected) and the risk of RSA. Odds ratios (ORs) and 95% confidence intervals (CIs) for codominant, dominant and recessive genetic models were assessed by RevMan software. Eight studies with 2813 cases and 2830 controls were included in this meta-analysis. The pooled analysis showed that − 2578C/A, − 1154G/A polymorphisms of VEGF were not significantly associated with the risk of RSA neither under codominant model nor under dominant model, nor under recessive model. Whereas, for − 634G/C polymorphism, the pooled OR and 95% CI were 1.23 (1.01–1.49) under recessive model; and for 936C/T polymorphism, the pooled OR and 95% CI were 1.34 (1.07–1.67) and 1.40 (1.09–1.80) under codominant and dominant models, respectively. This meta-analysis suggested that VEGF gene − 2578C/A, − 1154G/A polymorphisms were not significantly associated with the risk of RSA, whereas, − 634G/C and + 936C/T polymorphisms were associated with the risk of RSA under specific genetic models.     

VEGF gene polymorphism association with diabetic neuropathy

Vascular factors beside metabolic problems are involved in both etiopathogenesis of diabetic neuropathy, and more remarkably, later in “repair” phase, that governs the net balance between neuro-regenerative/degenerative reactions. Regarding ischemic nature of diabetic neuropathy that highlights necessity of blood vessels re-establishment during tissue healing, VEGF (vascular endothelial growth factor) has been recently the subject of extensive investigations in diabetic neuropathy (DNU). This growth factor possesses angiogenic potentials in addition to the hemodynamic functions. The distribution of VEGF gene polymorphisms at positions −7*C/T, −1001*G/C, −1154*G/A and −2578*C/A were analysed by ARMS–PCR in 248 type 1 diabetic British-Caucasian subjects (81 DNU+, 167 DNU−). We have found that distribution of a VEGF gene polymorphism at promoter region (−7*C/T) was significantly different between diabetic subjects with vs. without neuropathy and the allele (C) conferred susceptibility to DNU (P = 0.02; OR = 1.78, 95% CI 1.0–3.1). The present study indicates that polymorphism of the VEGF gene at position −7*C/T might be implicated in the pathogenesis of diabetic neuropathy as it may harbour some functional/regulatory potential in VEGF gene expression. However, this requires further studies in order to better understand its phenotypic impact and to investigate the prognostic value of this polymorphism in diabetic neuropathy as a chronic complication of diabetes.     

Identification of single-nucleotide polymorphism in the progesterone receptor gene and its association with reproductive traits in rabbits

A total of 598 F₂ does from a cross between the high and low lines selected divergently for uterine capacity during 10 generations were used in a candidate gene analysis. The presence of major genes affecting the number of implanted embryos and uterine capacity has been suggested in lines divergently selected for uterine capacity. Uterine capacity is a main component of litter size. The progesterone receptor gene was tested as a candidate gene to determine whether polymorphisms explain differences in litter size and its components. Fragments of the promoter region and exons 1–8 were amplified and sequenced. One SNP was found in the promoter region, 2464G>A, three SNPs in the 5′-UTR exon 1, and a silence SNP in exon 7. The first four SNPs were segregated in two haplotypes. The allele G found in the promoter region was found in 75% of the high-line parental animals and in 29% of the low-line parental animals. The GG genotype had 0.5 kits and 0.5 implanted embryos more than the AA genotype. At 48 hr of gestation, the difference in early embryo survival and embryonic stage of development was small. However, at 72 hr of gestation, the GG genotype had 0.36 embryos more than the AA genotype and also had a more advanced embryonic stage of development, showing a lower percentage of compacted morulae and a higher percentage of blastocysts. The difference in litter size between the GG and GA genotypes was similar to the difference found between homozygote genotypes; however, differences in implanted embryos, early embryo survival, and embryo development were not detected between the GG and GA genotypes.     

Association of the vascular endothelial growth factor (VEGF-1154G>A) polymorphism in patients with colorectal cancer

Angiogenesis plays a pivotal role in the development of colon cancer during the promotion and metastasis of tumor growth. Vascular endothelial growth factor (VEGF) is known to be a potent angiogenic factor. This hospital-based case-control study was carried out to decide where there existed an association between the VEGF-1154G>A polymorphism and the susceptibility to colon cancer. DNA samples taken from 278 colon cancer patients and 226 healthy controls were studied using with real-time PCR for VEGF-1154G>A polymorphism. Genotype frequencies of the VEGF-1154G>A polymorphism were significantly different between patient and control groups (adjusted OR=2.735, 95% CI=1.243?6.015 for AA vs. GG genotype). In addition, upon stratification by gender and age, the frequencies of the A allele-bearing genotypes significantly increased the risk for development of colon cancer in men and patients younger than 55 years (in men, adjusted OR=3.375, 95% CI=1.062?10.717, and in <55 years, adjusted OR=4.908, 95% CI=1.294?18.617). Also, upon stratification of patients with proximal and distal colon cancer individually, the association only showed these significant patterns in distal colon cancer. This study provides evidence that VEGF-1154G>A polymorphism, at least in Koreans, might be associated with risks of the colon cancer, particularly in males.     

Variant in sulfonylurea receptor-1 gene is associated with high insulin concentrations in non-diabetic Mexican Americans: SUR-1 gene variant and hyperinsulinemia

The high-affinity sulfonylurea receptor (SUR1) gene regulates insulin secretion and may play a role in type 2 diabetes. A silent variant in exon 31 of SUR1 (AGG→AGA) was detected by single-strand conformational polymorphism and genotypes were determined for 396 Mexican American subjects (289 non-diabetic). The normal and mutant alleles were designated G and A, respectively. Among non-diabetics, those with the AA genotype had higher fasting insulin values than those with the AG and GG genotypes (113.4 pmol/l for AA vs 82.8 pmol/l for AG/GG, P=0.043). Similar results were observed for 2-h insulin (849.6 pmοl/l for AA vs 498.6 pmol/l for AG/GG, P=0.0003) and for the proinsulin to specific insulin ratio (0.068 for AA vs 0.056 for AG/GG, P=0.030). Specific insulin levels also differed significantly across the three genotypic classes (P=0.021). No differences in fasting glucose, body mass index, or waist circumference according to genotype were noted. Two-hour glucose was modestly higher in individuals with the AA genotype. Since we have previously reported linkage between SUR1 and hyperglycemia, the present association between a SUR1 variant and hyperinsulinemia in normal individuals from a high diabetes risk ethnic group raises the possibility of primary insulin hypersecretion as an antecedent of type 2 diabetes in at least some individuals from this population. Received: 3 April 1998 / Accepted: 5 June 1998     

绝经后女性CYP19基因Val80及OPG基因A163G多态性与骨密度的相关性研究

探讨细胞色素P450 19 (CYP19) 基因Val80多态性及护骨素(OPG) 基因A163G多态性与绝经后女性骨密度 (BMD) 的关系。随机选择居住在重庆的绝经后女性200例, 采用多聚酶链反应-限制性片段长度多态性法检测Val80及A163G多态性, 采用Norland公司XR-46系列双能X线骨密度仪测量股骨近端及腰椎BMD。 200名绝经后女性中Val80基因型GG、GA及AA的频率分别为19.5％、44.5％及36.0％; A163G基因型GG、GC 及CC的频率分别为: 13.0％, 42.0％及45.0％; 基因型频率分布均符合Hardy-Weinberg平衡 (P＞0.05)。协方差分析及多元逐步回归分析显示CYP19基因第3外显子Val80多态性与绝经后女性BMD无相关性 (P＞0.05)。除大转子外, A163G位点AG/GG/AG+GG基因型者股骨颈、Ward’s三角及腰椎BMD均较AA基因型者低, A163G基因型与股骨颈、Ward’s三角及腰椎BMD有相关性 (P＜0.05)。OPG基因启动子区A163G多态性分布存在明显的种族差异, 且与绝经后女性BMD有一定关联, AA型对BMD具有一定的保护作用, G等位基因是BMD降低的危险因素。