Association of a polymorphic variant of the Werner helicase gene with myocardial infarction in a Japanese population

Ye, Lin; Miki, Tetsuro; Nakura, Jun; Oshima, Junko; Kamino, Kouzin; Rakugi, Hiromi; Ikegami, Hiroshi; Higaki, Jitsuo; Edland, Steven D.; Martin, George M.; Ogihara, Toshio

doi:10.1002/(sici)1096-8628(19970211)68:4<494::aid-ajmg30>3.0.co;2-l

Cited by 93 publications

(67 citation statements)

References 21 publications

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“…Codon WRN:1367 polymorphism did not show a significant association with non-insulin-dependent diabetes, as had been reported for a Japanese sample (11).…”

Section: Discussionsupporting

confidence: 78%

“…Our elderly population showed allele frequencies similar to those of populations of European origin and different from those of Japanese samples (11,12). In a Finnish population, the R allele frequency did not differ between newborns and centenarians, indicating the absence of a protective age-related effect of this allele.…”

Section: Discussionsupporting

confidence: 42%

“…Genotyping WRN:1367 polymorphism was analyzed using the method of Ye et al (11). A 193-bp sequence containing the polymorphic site was amplified by the polymerase chain reaction (PCR) using the following primers: sense: 5-'GCCTAATCAGAATGTTAGTT-3', antisense: 5'-TCAGTATTGATGCCTAC CTC-3'.…”

Section: Dna Extractionmentioning

confidence: 99%

“…Specific WRN polymorphisms have been studied to understand the impact of molecular variants on longevity in WS as well as other age-related disorders and can yield new insights to its biological and pathological role (3,4,8,11). The identification of genetic polymorphisms as risk factors for complex diseases in elderly people can be relevant for their prevention, diagnosis and prognosis.…”

Section: Introductionmentioning

confidence: 99%

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Frequency of Werner helicase 1367 polymorphism and age-related morbidity in an elderly Brazilian population

Smith

Silva

Araújo

et al. 2005

Braz J Med Biol Res

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Werner syndrome (WS) is a premature aging disease caused by a mutation in the WRN gene. The gene was identified in 1996 and its product acts as a DNA helicase and exonuclease. Some specific WRN polymorphic variants were associated with increased risk for cardiovascular diseases. The identification of genetic polymorphisms as risk factors for complex diseases affecting older people can improve their prevention, diagnosis and prognosis. We investigated WRN codon 1367 polymorphism in 383 residents in a district of the city of São Paulo, who were enrolled in an Elderly Brazilian Longitudinal Study. Their mean age was 79.70 ± 5.32 years, ranging from 67 to 97. This population was composed of 262 females (68.4%) and 121 males (31.6%) of European (89.2%), Japanese (3.3%), Middle Eastern (1.81%), and mixed and/or other origins (5.7%). There are no studies concerning this polymorphism in Brazilian population. These subjects were evaluated clinically every two years. The major health problems and morbidities affecting this cohort were cardiovascular diseases (21.7%), hypertension (83.7%), diabetes (63.3%), obesity (41.23%), dementia (8.0%), depression (20.0%), and neoplasia (10.8%). Their prevalence is similar to some urban elderly Brazilian samples. DNA was isolated from blood cells, amplified by PCR and digested with PmaCI. Allele frequencies were 0.788 for the cysteine and 0.211 for the arginine. Genotype distributions were within that expected for the Hardy-Weinberg equilibrium. Female gender was associated with hypertension and obesity. Logistic regression analysis did not detect significant association between the polymorphism and morbidity. These findings confirm those from Europeans and differ from Japanese population.

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“…Codon WRN:1367 polymorphism did not show a significant association with non-insulin-dependent diabetes, as had been reported for a Japanese sample (11).…”

Section: Discussionsupporting

confidence: 78%

Section: Discussionsupporting

confidence: 42%

Section: Dna Extractionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Frequency of Werner helicase 1367 polymorphism and age-related morbidity in an elderly Brazilian population

Smith

Silva

Araújo

et al. 2005

Braz J Med Biol Res

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“…Homozygosity for the T (Cys) allele of the T-C (Cys1367Arg) polymorphism of WRN was shown to be a risk factor for myocardial infarction in the Japanese population. 25,26 Our results now show that the variant C (Arg) allele of this polymorphism of WRN was protective against CKD. The À219G-T polymorphism of APOE was earlier associated with myocardial infarction in men in France and Northern Ireland, with the T allele representing a risk factor for this condition.…”

Section: Discussionsupporting

confidence: 52%

Association of candidate gene polymorphisms with chronic kidney disease in Japanese individuals with hypertension

et al. 2009

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Although hypertension has been recognized as a risk factor for chronic kidney disease (CKD), the genetic factors for predisposition to CKD in individuals with hypertension remain largely unknown. The purpose of this study was to identify the genetic variants that confer susceptibility to CKD among individuals with hypertension. The study population comprised 3696 Japanese individuals with hypertension (2265 men, 1431 women), including 1257 individuals (789 men, 468 women) with CKD (estimated glomerular filtration rate (eGFR) o60 ml min À1 per 1.73 m 2 ) and 2439 controls (1476 men, 963 women; eGFRX60 ml min À1 per 1.73 m 2 ). The genotypes for 30 polymorphisms of 26 candidate genes were determined. An initial screening of allele frequencies by the v 2 -test revealed that eight polymorphisms were significantly (false discovery rate o0.05) associated with the prevalence of CKD in hypertensive individuals. Subsequent multivariable logistic regression analysis with adjustment for covariates as well as a stepwise forward selection procedure revealed that the T-C (Val591Ala) polymorphism of APOB (rs679899), the À681C-G polymorphism of PPARG (rs10865710), the T-C (Cys1367Arg) polymorphism of WRN (rs1346044), the À850C-T polymorphism of TNF (rs1799724), the À219G-T polymorphism of APOE (rs405509), the C-T polymorphism of PTGS1 (rs883484) and the 41A-G (Glu14Gly) polymorphism of ACAT2 (rs9658625) were significantly (Po0.05) associated with the prevalence of CKD. Our results suggest that APOB, WRN, ACAT2, APOE, PPARG, TNF and PTGS1 are susceptibility loci for CKD among Japanese individuals with hypertension. Determination of the genotypes for these polymorphisms may prove informative for the assessment of genetic risk for CKD among such individuals.

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Nonvalidation of Reported Genetic Risk Factors for Acute Coronary Syndrome in a Large-Scale Replication Study

Morgan¹,

Krumholz²,

Lifton³

et al. 2007

JAMA

238

179

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Context Given the numerous, yet inconsistent, reports of genetic variants being associated with acute coronary syndromes (ACS), there is a need for comprehensive validation of ACS susceptibility genotypes.Objective To perform an extensive validation of putative genetic risk factors for ACS.Design, Setting, and Participants Through a systematic literature search of articles published before March 10, 2005, we identified genetic variants previously reported as significant susceptibility factors for atherosclerosis or ACS. Restricting our analysis to white patients to reduce confounding from racial admixture, we identifed 811 patients who presented from March 2001 through June 2003 with ACS at 2 Kansas City, Mo, universityaffiliated hospitals. During 2005-2006, we genotyped the 811 patients along with 650 age-and sex-matched controls for 85 variants in 70 genes and attempted to replicate previously reported associations. We further explored possible associations without prior assumption of specific risk models and used the Sign test to search for weak associations. Main Outcome MeasuresCompare each prespecified gene variant associated with ACS risk among cases and controls. A surplus of associations would imply that some are associated with ACS. ResultsOf 85 variants tested, only 1 putative risk genotype (−455 promoter variant in ␤-fibrinogen) was nominally statistically significant (P=.03). Only 4 additional genes were positive in model-free analysis. Neither number of associations was more frequent than expected by chance, given the number of comparisons. Finally, only 41 of 84 predefined risk variants were even marginally more frequent in cases than in controls (with 1 tie), representing a 48.8% "win rate" (95% confidence interval, 38.1%-59.5%) for the collective risk genotypes (P=.91, Sign test). ConclusionsOur null results provide no support for the hypothesis that any of the 85 genetic variants tested is a susceptibility factor for ACS. These results emphasize the need for robust replication of putative genetic risk factors before their introduction into clinical care.

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Association of a polymorphic variant of the Werner helicase gene with myocardial infarction in a Japanese population

Cited by 93 publications

References 21 publications

Frequency of Werner helicase 1367 polymorphism and age-related morbidity in an elderly Brazilian population

Frequency of Werner helicase 1367 polymorphism and age-related morbidity in an elderly Brazilian population

Association of candidate gene polymorphisms with chronic kidney disease in Japanese individuals with hypertension

Nonvalidation of Reported Genetic Risk Factors for Acute Coronary Syndrome in a Large-Scale Replication Study

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