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1.
Petry CJ Seear RV Wingate DL Acerini CL Ong KK Hughes IA Dunger DB 《Human genetics》2011,130(5):663-670
This study was designed to test the hypothesis that polymorphic variation in maternally transmitted foetal H19 alleles is associated with offspring size at birth and alterations in maternal glucose concentrations in pregnancy. Inferred
parent of origins of transmitted alleles from 13 haplotype tag SNPs in the H19 gene region from 845 family (mother, partner, offspring) trios from the prospective Cambridge Baby Growth Study and 315 trios
from the retrospective Cambridge Wellbeing Study cohorts were tested for association with offspring size at birth measures,
as well as maternal glucose concentrations 1 h after a glucose load at week 28 of pregnancy. The foetal rs2071094 allele inherited
from the mother was associated with increased birth weight (p = 0.0015) adjusted for gestational age, parity and sex. In the Cambridge Baby Growth Study it was also associated with increased
head circumference (p = 0.004), length (p = 0.017) and sum of skinfold thicknesses (p = 0.017) at birth. In contrast to these results there was no association between offspring birth weight and either the maternal
rs2071094 genotype or the foetal allele from the father. None of the foetal alleles or maternal genotypes were associated
with maternal glucose concentrations, neither were there any other associations with offspring birth weight. In conclusion,
consistent with imprinting, common polymorphic variation in foetal H19 alleles transmitted only from the mother are associated with birth weight and other markers of size at birth. Polymorphic
variation in H19 is not associated with significant changes in maternal glucose tolerance in the third trimester of pregnancy. 相似文献
2.
Gaudet MM Lacey JV Lissowska J Peplonska B Brinton LA Chanock S Garcia-Closas M 《Human genetics》2008,123(2):155-162
Genetic variation in CYP17 is suspected to be related to endometrial cancer risk based on its role in the regulation of steroid and non-steroid hormone
biosynthesis. Reported associations between CYP17 and higher levels of estradiol in some studies suggest that the C allele of a T-to-C single nucleotide polymorphism (SNP)
in the 5′UTR of CYP17 (rs743572) may be associated with an increased risk of hormone-related cancers. However, five relatively small epidemiologic
studies of endometrial cancer have reported that women with the rs743572 C allele have a decreased risk of endometrial cancer.
To examine this association, we genotyped rs743572 and eight other haplotype-tagging SNPs (htSNPs), which are estimated to
capture >80% of the variation in CYP17 in a population-based study of 497 endometrial cancer cases and 1,024 controls in Poland. Significant associations were not
found for rs743572 (per C allele: OR = 1.12, 95%CI 0.96–1.30; P-trend = 0.15), for individual htSNPs, or for extended haplotypes (global P-value = 0.60). When we pooled data from previously published studies with our own (a total of 1,004 endometrial cases and
1,907 controls), we observed significant study heterogeneity in summary estimates of the association between rs743572 and
endometrial cancer, as well as evidence of publication bias. In conclusion, our data are not consistent with a decreased endometrial
cancer risk associated with rs743572, as previously reported, or with other haplotype-tagging polymorphisms. Further evaluation
in consortia is necessary to confirm potential weak associations between common variation in CYP17 and endometrial cancer risk and to address the concern of publication bias.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
3.
Adolescent idiopathic scoliosis (AIS) is a complex disorder with an unclear etiology and pathogenesis. In previous studies,
genome-wide linkage and genetic association analyses have been carried out to find genetic factors linked with AIS. In this
study, we examined whether the susceptibility to AIS is associated with MATN1 gene polymorphisms in a Korean population, which included 166 individuals with AIS and 126 controls. We found that there
were no statistically significant associations between any of the MATN1-linked allele or genotype frequencies between AIS and controls. However, statistically significant associations were found
at single nucleotide polymorphism (SNP) rs1065755 when comparing the curve patterns of AIS with the controls. The A allele
of SNP rs1065755 was associated with a higher risk of AIS than the allele G in the genotype–phenotype (curve pattern) analysis
(P = 0.029). In addition, the frequency of the A allele of SNP rs1065755 in AIS with double major curves was higher than in
controls (P = 0.021, ORs = 2.56 within 95% CI = 1.12–5.83). Additionally, among the predicted common haplotypes, the frequency of the
haplotype GATT (31.3%) in AIS with double major curves was higher than in controls (15.2%) (P = 0.024, ORs = 2.54 within 95% CI = 1.11–5.84). We conclude that the A allele of SNP rs1065755 in the MATN1 gene is associated with AIS. 相似文献
4.
Hao Mei Wei Chen Sathanur R. Srinivasan Fan Jiang Nicholas Schork Sarah Murray Erin Smith Joanne D. So Gerald S. Berenson 《Human genetics》2010,128(6):589-596
SNP rs9939609 within the fat mass and obesity associated gene (FTO) is strongly associated with adult body mass index (BMI).
However, influences of FTO on longitudinal BMI change from childhood to adulthood have not been examined. Knowledge is limited
on FTO, modulating the association between birth weight and longitudinal change of BMI. This longitudinal study examined SNPs
of FTO in 658 white subjects from childhood (3–17 years) to adulthood (18–45 years). No significant associations of FTO SNPs
with either birth weight or longitudinal BMI over childhood were noted after multiple-test adjustment. However, three SNPs
(rs9939609, rs17820875 and rs860713) with different inheritance patterns were identified to be associated with longitudinal
BMI over adulthood after Bonferroni adjustment (P = 5.3 × 10−5, 2.0 × 10−4 and 0.001). In addition, interactions were discovered between birth weight and SNPs of rs17820875 (P = 0.001) and rs860713 (0.002). A negative association between birth weight and adult BMI were found in risk genotype AG of
rs17820875 and GG of rs860713 in contrast to positive associations in other genotypes. These findings led to the conclusion
that lower birth weight predisposes to higher adult BMI depending on FTO risk genotypes. Our studies underscore the importance
of FTO influences on obesity and provide insights into the evolution of the long-term burden of obesity. 相似文献
5.
Munshi A Sharma V Kaul S Al-Hazzani A Alshatwi AA Shafi G Koppula R Mallemoggala SB Jyothy A 《Molecular biology reports》2012,39(2):1677-1682
Genetic variants of cytochrome P450 4F2 (CYP4F2) gene have been suggested to be risk factors for hypertension, cardiovascular
diseases and stroke. In the present case–control study we investigated the association of 1347 G/A polymorphism (rs2108622)
in the 11th exon region of CYP4F2 gene with hypertension, ischemic stroke and stroke subtypes classified according to TOAST
(Trial of Org 10172 in Acute Stroke Treatment) classification. Five hundred and seven stroke patients (hypertensives: normotensives = 279:228)
and four hundred and eighty seven, age and sex matched controls (males: females = 356:131) (hypertensives: normotensives = 148:339)
were involved in the study. The genotypes were determined by PCR-RFLP technique. Genotypes were confirmed by subjecting the
PCR products to sequencing. Significant difference was observed in the genotypic distribution and allelic frequency between
the stroke patients and healthy controls. AA genotype and A allele associated significantly with stroke and hypertension [P = 0.009; OR = 1.59 (95% CI = 1.119–2.283) and P = 0.010; OR = 1.26 (95% CI = 1.056–1.502); P = 0.01; OR = 1.58 (95% CI = 1.11–2.272) and P = 0.010; OR = 1.25(95% CI = 1.054–1.504) respectively]. A stepwise logistic regression analysis confirmed these findings.
To establish that this polymorphism is associated with stroke independent of hypertension; we compared stroke patients without
hypertension with normotensive controls. Significant difference was observed in genotypic distribution and allelic frequency
between the two groups (P = 0.001 and 0.002 respectively). Evaluating the association of this polymorphism with stroke subtypes we found significant
associations with cardioembolic stroke (P < 0.001). In conclusion our study suggests that 1347A allele of CYP4F2 gene is an important risk factor for hypertension
and ischemic stroke. 相似文献
6.
Xing Gu Peng Qi Feiguo Zhou Qiang Ji Hao Wang Tonghai Dou Yunpeng Zhao Chunfang Gao 《Human genetics》2010,127(1):75-81
Corticotropin-releasing hormone receptor 2 (CRHR2) plays a role in both the central nervous system (CNS) and the peripheral
nervous system. CRHR2 together with its ligands, urocortins (Ucns) and corticotropin-releasing hormone (CRH), functions as
a mediator of inflammatory response and inhibitor of angiogenesis. Recently, it has been reported to be expressed in many
human cancers. An association between rs2267716 polymorphism in the CRHR2 gene and susceptibility to hepatocellular carcinoma (HCC) was found in patients with chronic hepatitis C virus (HCV) infection.
In the present study we analyzed, using a polymerase chain reaction–ligation detection reaction (PCR–LDR), the rs2267716 polymorphism
in 364 hepatitis B virus (HBV)-related HCC patients, 196 non-HCC patients with HBV infection, and 404 healthy controls. The
aim was to detect the possible association of this single-nucleotide polymorphism (SNP) with susceptibility to HBV-related
HCC. Significant differences of rs2267716 allele were detected between HBV-related HCC patients and healthy controls (OR = 1.55,
95% CI 1.13–2.15, P = 0.007) or non-HCC patients with HBV infection (OR = 1.61, 95% CI 1.13–2.31, P = 0.009). These results suggest that the rs2267716 polymorphism in the CRHR2 gene might influence the risk of developing HCC in patients with HBV infection in Chinese population. 相似文献
7.
The aim of our meta-analysis was to quantitatively summarize the association of TYK2 gene polymorphisms with autoimmune and
inflammatory diseases. 11 studies that included data from 21497 cases and 22647 controls were identified. OR was used as a
measure of the effect of the association in a fixed/random effect model. Meta-analysis was performed for six TYK2 gene polymorphisms
(rs34536443, rs2304256, rs280523, rs280519, rs12720270 and rs12720356). Significant association was found in rs34536443 (C
versus G: OR = 0.76, 95% CI = 0.69–0.84, P < 0.00001; GC + CC versus GG: OR = 0.78, 95% CI = 0.68–0.90, P = 0.0005; CC versus GG + GC: OR = 0.76, 95% CI = 0.28–2.05, P = 0.58; CC versus GG: OR = 0.74, 95% CI = 0.27–2.02, P = 0.56; GC versus GG: OR = 0.78, 95% CI = 0.68–0.90, P = 0.0006) and rs2304256 (A versus C: OR = 0.78, 95% CI = 0.70–0.87, P < 0.0001; CA + AA versus CC: OR = 0.69, 95% CI = 0.59–0.81, P < 0.0001; AA versus CC + CA: OR = 0.75, 95% CI = 0.66–1.00, P = 0.05; AA versus CC: OR = 0.64, 95% CI = 0.47–0.86, P = 0.003; CA versus CC: OR = 0.70, 95% CI = 0.60–0.83, P < 0.0001) in TYK2 gene, but not for the other polymorphisms (rs280523, rs280519, rs12720270, and rs12720356). This meta-analysis
demonstrates that autoimmune and inflammatory diseases is associated with TYK2 gene rs34536443 and rs2304256 polymorphisms,
but not rs280523, rs280519, rs12720270 and rs12720356. 相似文献
8.
Kusinska R Górniak P Pastorczak A Fendler W Potemski P Mlynarski W Kordek R 《Molecular biology reports》2012,39(3):2915-2919
Breast cancer is a major cause of cancer-related deaths in women. It is known that obesity is one of the risk factors of breast
cancer. The subject of our interest was genes: FTO, MC4R and NRXN3–associated with obesity. In this study we have analyzed frequencies of genomic variants in FTO, MC4R and NRXN3 in the group of 134 breast cancer patients. We genotyped two polymorphic sites located in FTO gene (rs993909 and rs9930506), one polymorphic site of MC4R gene (rs17782313) and one polymorphic site of NRXN3 gene (rs10146997). Our hypothesis was that above mentioned SNPs could participate in carcinogenesis. Our research has showed
that only rs10146997 was significantly (P = 0.0445) associated with higher risk of breast cancer development (OR = 0.66 (95% CI 0.44–0.99)). Moreover, G allele carriers
in rs10146997 of the NRXN3 gene were the youngest patients at onset of breast cancer. On the basis of our research we suggest that further functional
may elucidate the role of genomic variation in breast cancer development. 相似文献
9.
Ranjzad F Mahmoudi T Irani Shemirani A Mahban A Nikzamir A Vahedi M Ashrafi M Gourabi H 《Molecular biology reports》2012,39(3):2313-2319
In this study, we explored whether polymorphisms in insulin receptor (INSR), adiponectin (ADIPOQ), parathyroid hormone (PTH),
and vitamin D receptor (VDR) genes are associated with polycystic ovary syndrome (PCOS). A total of 362 subjects, including
181 women with PCOS and 181 controls were enrolled in this case-control study. Two SNPs (rs2059806 and rs1799817) in the INSR
gene, two SNPs (rs2241766 and rs1501299) in the ADIPOQ gene, one SNP (rs6256) in the PTH gene, and one SNP (rs757343) in the
VDR gene were analyzed using PCR-RFLP method. We observed no significant difference in genotype and allele frequencies between
the women with PCOS and controls for the rs2059806, rs1799817, rs1501299, rs6256, and rs757343 polymorphisms either before
or after adjustment for confounding factors including age and BMI. However, the ADIPOQ rs2241766 “TT” genotype compared with
“TG and GG” genotypes was associated with a 1.93-fold increased risk for PCOS (P = 0.006, OR = 1.93, 95% CI = 1.20–3.11), and the differences remained significant after adjustment for age and BMI (P = 0.039, OR = 1.72, 95% CI = 1.03–2.86). Furthermore, the ADIPOQ rs2241766 “T” allele was significantly overrepresented in
women with PCOS than controls (P = 0.006; OR = 1.80, 95% CI = 1.18–2.70), and the difference remained significant after Bonferroni correction. Our findings
suggest that the ADIPOQ rs2241766 “TT” genotype is a marker of increased PCOS susceptibility. This study also indicates for
the first time that there are no significant association between INSR rs2059806, PTH rs6256, and VDR rs757343 gene polymorphisms
and PCOS risk. However, these data remain to be confirmed in larger studies and in other populations. 相似文献
10.
Background Two single nucleotide polymorphisms (SNPs, rs10757278 and rs2383207) on chromosome 9p21 have been proved to be associated
with myocardial infarction. We investigated whether these two genetic markers are determinants of early-onset coronary artery
disease. Methods and results A total of 444 consecutive patients were studied including 212 cases with coronary stenosis ≥50% or previous myocardial infarction and 232 controls without documented coronary artery disease. Ligase detection reaction
was performed to detect two SNPs. After adjustment of clinical parameters, significant associations were identified for the
rs2383207 and rs10757278 SNPs, with A/G and G/G genetypes at rs10757278 and G/G genetype carriers at rs2383207 having a higher
risk of early-onset coronary artery disease than carriers of A/A genotype (odds ratio [OR] 2.207, 95% CI: 1.069–4.394, P = 0.028; OR 3.051, 95% CI: 1.086–8.567, P = 0.004; OR 2.964, 95% CI: 1.063–8.265, P = 0.038, respectively). There were no associations between rs10757278 and rs2383207 genotypes and the severity of coronary
artery disease (both P > 0.05). Conclusions The rs10757278 and rs2383207 variants are determinants for early-onset coronary artery disease. These markers may help the
identification of patients at increased risk for early-onset coronary artery disease.
Zhong Chen and Qi Qian contributed equally to this paper. 相似文献
11.
To replicating the associations of type 2 diabetes (T2D) and six novel reported variants in Han Chinese lean individuals of
first episode T2D, a total of six high risk single nucleotide polymorphisms (SNPs) from the BCL11A, DUSP9, IRS1, CENTD2, ADRA2A, and CDKAL1 genes were examined. Candidate six SNPs were genotyped in 761 T2D patients and 433 control subjects, and associations between
the six SNPs and Body Mass Index (BMI), Fasting Plasma Glucose (FPG) and Two Hours Oral Glucose Tolerance Test (2hOGTT) were
also investigated. CDKAL1 provided the strongest evidence for replication, where rs7754840 was associated with T2D (odds ratio = 1.54, per copy of
the risk C allele, P = 8.10 × 10−7). SNP rs5945326 at DUSP9 showed modest significance (odds ratio = 0.81, per copy of the protective G allele, P = 0.02). After adjusting the confounders of age, gender and BMI, the above results remain significant for both rs7754840
(P < 1.0 × 10−4) and rs5945326 (P = 0.043) respectively. After correcting for multiple testing, however, only the association between T2D and rs7754840 at
CDKAL1 (P < 1×10−4) remains significant. In addition, the risk C allele of CDKAL1 rs7754840 was significantly associated with increased FPG levels (P = 3.8 × 10−4). The association between genetic variant in CDKAL1 gene was detected in the Han Chinese lean individuals. The correlation between rs7754840-C allele and increased FPG levels
is consistent with the potential function of CDKAL1 gene in pancreatic islets. 相似文献
12.
Peeters AV Beckers S Verrijken A Mertens I Roevens P Peeters PJ Van Hul W Van Gaal LF 《Human genetics》2008,124(4):431-436
The sirtuin SIRT1 is an important regulator of energy metabolism through its impact on glucose and lipid metabolism and therefore
we tested the hypothesis that genetic variation in SIRT1 may have an effect on adiposity in a Belgian case/control association study. This study included 1,068 obese patients (BMI ≥ 30 kg/m2) from the outpatient obesity clinic and 313 lean controls (BMI between 18.5 and 25 kg/m2). Anthropometrics were assessed by classical methods and visceral (VFA), subcutaneous (SFA) and total abdominal (TFA) fat
areas were determined by a CT scan. The extent of linkage disequilibrium in SIRT1 allowed us to reduce the number of SNPs to two, sufficient to cover the entire gene. The two tagSNPs (rs7069102 and rs3818292)
were analyzed by LightSNiP assays in all subjects. Rs3818292 genotypes were similarly distributed in cases and controls, whereas
rs7069102 was different for the additive (P = 0.007) and dominant (P = 0.01) model. The variant C-allele of rs7069102 reduced obesity risk with an OR of 0.74 (P = 0.025; 95% CI 0.57–0.96) under a dominant model. In obese male subjects, this variant allele was associated with increased
waist circumference (P = 0.04), WHR (P = 0.02), TFA (P = 0.03) and VFA (P = 0.005) (dominant model; adjusted for age and BMI). Rs3818292 was related to VFA (P = 0.005; adjusted for age and BMI) in obese males while in obese women, no significant associations were detected. Our data
suggest that genetic variation in SIRT1 increases the risk for obesity, and that SIRT1 genotype correlates with visceral obesity parameters in obese men.
A. V. Peeters and S. Beckers have contributed equally to this work. 相似文献
13.
Cook MB Graubard BI Quraishi SM Yeager M Chanock SJ Crenshaw A Erickson RL Rubertone MV Thomas G McGlynn KA 《Human genetics》2008,123(4):409-418
Much evidence supports the premise that population genetic variation contributes significantly to the risk of testicular germ-cell
tumor (TGCT). However, investigations of the association between genomic markers and TGCT susceptibility are scarce. Single
nucleotide polymorphisms (SNPs) at the locus 8q24 have recently been found to be associated with prostate, colorectal and
breast cancer. The US Servicemen’s testicular tumor environmental and endocrine determinants (STEED) study was used to investigate
the association of 15 specific 8q24 SNPs with TGCT and its two main histologic groups of seminoma and nonseminoma. Conditional
and unconditional logistic regression models, adjusted for the matching variables of year of birth, race/ethnicity and serum
date, were utilized to produce odds ratios (OR) and 95% confidence intervals (95%CI). The analysis included 680 controls and
568 TGCT cases. In the TGCT analysis, no SNP was associated with risk in both heterozygotes and variant homozygotes. When
stratified by histology the seminoma analysis also showed no association with the 8q24 SNPs. Conversely, the analysis of nonseminomas
had three tentative associations (rs6470494, ORgenotype AG = 1.15, 95%CI: 0.86–1.54; ORgenotype GG = 1.68, 95%CI: 1.04–2.73; p for trend = 0.04) (rs13254738, ORgenotype GT = 1.04, 95%CI: 0.77–1.40; ORgenotype TT = 1.62, 95%CI: 1.06–2.49; p for trend = 0.07) (rs10505476, ORgenotype CT = 0.67, 95%CI: 0.50, 0.91; ORgenotype TT = 0.81, 95%CI: 0.47–1.39; p for trend = 0.04). There was no linkage disequilibrium between any of the 8q24 SNPs analyzed in this population. In conclusion,
this study has found little evidence for an association between the reported 8q24 SNPs and TGCTs, although the findings for
nonseminoma may be worth further investigation. 相似文献
14.
Paraoxonase is an HDL-associated enzyme that plays a preventive role against oxidative stress, which is thought to contribute
to cancer development. PON1 activity varies widely among individuals, which is in part related to two common nonsynonymous
polymorphisms in the PON1 gene (Q192R and L55M). The polymorphisms in PON1 have been implicated in cancer risk. However, results
from the studies to date have been conflicting. To clarify the association, a meta-analysis was performed for 7,073 cases
and 9,520 controls from 25 published case–control studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used
to assess the strength of the association. Significant associations between PON1-L55M but not Q192R polymorphism and total
cancer were observed from all the comparisons. In stratified analyses, PON1-55M allele was a risk factor for breast cancer.
Similarly, increased risk was observed for prostate cancer (OR = 1.18, 95% CI: 1.01–1.36, P
heterogeneity = 0.260) and Caucasian population (OR = 1.18, 95% CI: 1.02–1.38, P
heterogeneity = 0.1) of the LM genotype, compared with the LL genotype. For PON1-Q192R polymorphism, PON1-192R allele was a decreased risk
factor for cancer in the Asian group (RR vs QQ: OR = 0.61, 95% CI: 0.38–0.98, P
heterogeneity = 0.268; QR vs QQ: OR = 0.71, 95% CI: 0.52–0.96, P
heterogeneity = 0.130; RR + QR vs QQ: OR = 0.71, 95% CI: 0.53–0.95, P
heterogeneity = 0.135). Although some modest bias could not be eliminated, this meta-analysis suggests that the PON1-55M allele is a risk factor for the development of cancer, in particular for breast cancer. Future studies with larger sample
sizes are warranted to further evaluate these associations. 相似文献
15.
Many studies have investigated the association between the CYP2E1 5′-flanking region (RsaI/PstI) polymorphism and head and neck cancer susceptibility, but the results were conflicting. In
this meta-analysis, we assessed 24 published studies involving 12,562 subjects of the association between CYP2E1 RsaI/PstI polymorphism and head and neck cancer risk. Using the fixed effects model, we found significant association between
PstI/RsaI polymorphism and head and neck cancer risk [OR = 1.11 (95%CI: 1.00–1.22) for c2 allele (P = 0.04) and OR = 1.57 (95% CI: 1.14–2.15) for c2 homozygous (P = 0.006) compared with wild type homozygote]. Significant results were also found in East Asians and Mix populations when
stratified by ethnicity. However, no significant associations were found for Caucasians in all genetic models. Stratified
analyses according to source of controls, significant associations were found only in hospital base controls. In the subgroup
analyses by tumor types, significant association was detected only in oral cancer group, while no significant associations
among laryngeal- or pharyngeal- cancer subgroup. This meta-analysis suggests that the CYP2E1 RsaI/PstI polymorphism may be a risk factor for head and neck cancer in Asians and Mix population, and that different carcinogenic
processes involved in the genesis of various tumor types may exist. 相似文献
16.
Yuanyuan Liu Min Ke Ming Yan Shuren Guo Mane Emily Mothobi Qiang Chen Fang Zheng 《Molecular biology reports》2011,38(2):1301-1307
GJA8 plays an important role in lens growth and transparency. Therefore, we hypothesized that two single nucleotide polymorphisms
(SNPs) in GJA8 might be associated with age-related cataract. We investigated the SNPs rs1495960 and rs9437983 using polymerase chain reaction-restriction
fragment length polymorphism (PCR-RFLP) and DNA sequencing, in 96 age-related cataract patients, and 208 gender- and age-matched
healthy controls. No significant differences between cases and controls were seen in genotype or allele distributions of rs1495960
(P > 0.05). The allele distribution of rs9437983 was different between cases and controls, but no difference was detected in
its genotype distribution. Cataract patients had a significantly lower G–G haplotype frequency (4.9% vs. 15.5%, P = 0.0001), and a significantly higher G–A haplotype frequency (45.6% vs. 36.4%, P = 0.030) than controls. Limiting to nuclear cataract cases significantly increased the differences between cases and controls
for G–G and G–A haplotypes. These results support that the GJA8 gene may be a novel susceptibility gene for age-related cataracts. 相似文献
17.
The vascular endothelial growth factor (VEGF) gene has been suggested to play an important role in the pathogenesis of age-related macular degeneration (AMD). However,
the results have been inconsistent. In this study, we performed a meta-analysis to clarify the associations between VEGF polymorphisms and AMD risk across different populations. Published literature from PubMed and EMBASE were retrieved. Pooled
odds ratio (OR) with 95% confidence interval (CI) was calculated using fixed- or random-effects model. Five studies (1,280
cases and 715 controls) for rs833061 polymorphism, five studies (1,033 cases and 807 controls) for rs1413711 polymorphism,
and four studies (1,217 cases and 4,079 controls) for rs2010963 polymorphism were identified. No statistically significant
association was found for rs833061, rs1413711 and rs2010963 polymorphisms, although there were significant associations for
rs833061 polymorphism under a homogeneous co-dominant model (CC vs. TT: OR = 1.59, 95%CI 1.14–2.23) and for rs1413711 polymorphism
under a recessive model (TT vs. CT + CC: OR = 1.50, 95%CI 1.08–2.08), the results were not robust by sensitivity analysis.
However, there was a significant association for rs833061 among European and East Asian populations, and for rs1413711 among
Europeans. The present meta-analyses indicated that there were no significantly associations between VEGF polymorphisms (rs833061, rs1413711, rs2010963) and the risk of AMD, although the association was different for each polymorphism
among different populations. 相似文献
18.
The aim of this study was to determine whether the vitamin D receptor (VDR) polymorphisms confer susceptibility to rheumatoid
arthritis (RA) and systemic lupus erythematous (SLE). A meta-analysis was conducted on the associations between the BsmI,
TaqI, FokI, and ApaI polymorphisms of VDR and RA or SLE using: (1) allele contrast, (2) the recessive model, (3) the dominant
model, and (4) additive model. A total of ten studies, six RA and four SLE studies, were considered in the meta-analysis.
Meta-analysis of the VDR BsmI and TaqI polymorphisms showed no association between RA in all subjects, or in European or Asian
subjects. In contrast, meta-analysis of the F allele, the FF genotype, and the FF vs. the ff genotype of the FokI polymorphism
showed significant associations with RA in Europeans. The overall OR of the association between the F allele and RA was 1.502
(95% CI = 1.158–1.949, P = 0.002). Meta-analysis of the B allele, BB + Bb genotype, and BB genotype (additive model) of the BsmI polymorphism showed
significant associations with SLE and LN in Asians. The overall ORs of the associations between the B allele and SLE and LN
were 3.584 (95% CI = 1.407–9.130, P = 0.007) and 3.652 (95% CI = 1.347–9.902, P = 0.011). This meta-analysis demonstrates that the VDR FokI polymorphism may confer susceptibility to RA in Europeans. Furthermore,
associations were found between the VDR BsmI polymorphism and susceptibilities to SLE and LN in Asians. 相似文献
19.
Alexander M. Kulminski Yury Loika Irina Culminskaya Jian Huang Konstantin G. Arbeev Olivia Bagley Mary F. Feitosa Joseph M. Zmuda Kaare Christensen Anatoliy I. Yashin 《Aging cell》2019,18(1)
The TOMM40‐APOE variants are known for their strong, antagonistic associations with Alzheimer's disease and body weight. While a stronger role of the APOE than TOMM40 variants in Alzheimer's disease was suggested, comparative contribution of the TOMM40‐APOE variants in the regulation of body weight remains elusive. We examined additive effects of rs2075650 and rs157580 TOMM40 variants and rs429358 and rs7412 APOE variants coding the ε2/ε3/ε4 polymorphism on body mass index (BMI) in age‐aggregated and age‐stratified cohort‐specific and cohort‐pooled analysis of 27,863 Caucasians aged 20–100 years from seven longitudinal studies. Minor alleles of rs2075650, rs429358, and rs7412 were individually associated with BMI (β = ?1.29, p = 3.97 × 10?9; β = ?1.38, p = 2.78 × 10?10; and β = 0.58, p = 3.04 × 10?2, respectively). Conditional analysis with rs2075650 and rs429358 identified independent BMI‐lowering associations for minor alleles (β = ?0.63, p = 3.99 × 10?2 and β = ?0.94, p = 2.17 × 10?3, respectively). Polygenic mega‐analysis identified additive effects of the rs2075650 and rs429358 heterozygotes (β = ?1.68, p = 3.00 × 10?9), and the strongest BMI‐lowering association for the rs2075650 heterozygous and rs429358 minor allele homozygous carriers (β = ?4.11, p = 2.78 × 10?3). Conditional analysis with four polymorphisms identified independent BMI‐lowering (rs2075650, rs157580, and rs429358) and BMI‐increasing (rs7412) associations of heterozygous genotypes with BMI. Age‐stratified conditional analysis revealed well‐powered support for a differential and independent association of the rs429358 heterozygote with BMI in younger and older individuals, β = 0.58, 95% confidence interval (CI) = ?1.18, 2.35, p = 5.18 × 10?1 for 3,068 individuals aged ≤30 years and β = ?4.28, CI = ?5.65, ?2.92, p = 7.71 × 10?10 for 6,052 individuals aged >80 years. TOMM40 and APOE variants are independently and additively associated with BMI. The APOE ε4‐coding rs429358 polymorphism is associated with BMI in older individuals but not in younger individuals. 相似文献