Significant association between PTPN11 polymorphism and gastric atrophy among Japanese Brazilians

Kawai, Shinya; Goto, Yasuyuki; Ito, Lucy S.; Oba-Shinjo, Sueli Mieko; Uno, Miyuki; Shinjo, Samuel Katsuyuki; Marie, Suely K.N.; Ishida, Yoshiteru; Nishio, Kenji; Naito, Mariko; Hamajima, Nobuyuki

doi:10.1007/s10120-006-0391-6

Cited by 13 publications

(19 citation statements)

References 37 publications

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“…This is in accordance with our hypothesis that gastric atrophy development after cagA -positive H. pylori infection was rarer among those with A/A genotype than among those with G/G genotype [24,25], although the significant association was observed only for severe gastric atrophy in this study. Since the biological processes in infection, atrophy development, and carcinogenesis are different [15], the association of this polymorphism with only atrophic development seemed biologically plausible.…”

Section: Discussionsupporting

confidence: 93%

“…In our previous studies among Japanese and Japanese Brazilians, the AA genotype in intron 3 was shown to reduce the risk of gastric atrophy development [24,25]. Recently, another PTPN11 SNP (rs11066322 at intron 10 in complete linkage disequilibrium to rs2301756) was found to be significantly associated with serum apoB levels in a British population [26], supporting the hypothesis that this PTPN11 polymorphism is functional.…”

Section: Introductionmentioning

confidence: 75%

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Associations of a PTPN11 G/A polymorphism at intron 3 with Helicobactor pyloriseropositivity, gastric atrophy and gastric cancer in Japanese

et al. 2009

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BackgroundPrevious studies have revealed the significance of Helicobacter pylori (H. pylori) infection as a risk factor of gastric cancer. Cytotoxin-associated gene A (cagA) positivity has been demonstrated to determine the clinical outcome of H. pylori infection in the presence of SHP-2 (src homology 2 domain-containing protein tyrosine phosphatase-2). This study aimed to examine the formerly reported association of G/A PTPN11 (protein-tyrosine phosphatase, nonreceptor-type 11) polymorphism (rs2301756) with gastric atrophy, as well as the association with gastric cancer in a Japanese population using a large sample size.MethodsStudy subjects were 583 histologically diagnosed patients with gastric cancer (429 males and 154 females) and age- and sex-frequency-matched 1,636 non-cancer outpatients (1,203 males and 433 females), who visited Aichi Cancer Center Hospital between 2001–2005. Serum anti-H. pylori IgG antibody and pepsinogens were measured to evaluate H. pylori infection and gastric atrophy, respectively. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by a logistic model.ResultsAmong H. pylori seropositive non-cancer outpatients, the age- and sex-adjusted OR of gastric atrophy was 0.82 (95% CI 0.62–1.10, P = 0.194) for G/A, 0.84 (95% CI 0.39–1.81, P = 0.650) for A/A, and 0.83 (95% CI 0.62–1.09, P = 0.182) for G/A+A/A, relative to G/G genotype, and that of severe gastric atrophy was 0.70 (95% CI 0.47–1.04, P = 0.079), 0.56 (95% CI 0.17–1.91, P = 0.356), and 0.68 (95% CI 0.46–1.01, P = 0.057), respectively. Among H. pylori infected subjects (H. pylori seropositive subjects and seronegative subjects with gastric atrophy), the adjusted OR of severe gastric atrophy was further reduced; 0.62 (95% CI 0.42–0.90, P = 0.012) for G/A+A/A. The distribution of the genotype in patients with gastric cancer was not significantly different from that for H. pylori infected subjects without gastric atrophy.ConclusionOur study results revealed that those with the A/A genotype of PTPN11 rs2301756 polymorphism are at lower risk of severe gastric atrophy, but are not associated with a decreased risk of gastric cancer, which partially supported our previous finding that the polymorphism in the PTPN11 gene encoding SHP-2 was associated with the gastric atrophy risk in H. pylori infected Japanese. The biological roles of this PTPN11 polymorphism require further investigation.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 75%

Associations of a PTPN11 G/A polymorphism at intron 3 with Helicobactor pyloriseropositivity, gastric atrophy and gastric cancer in Japanese

et al. 2009

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“…These are similar to the percentages found in our two previous studies of Japanese (68, 29 and 4%) (15) and Japanese-Brazilian (66, 30 and 4%) (20) populations. Data from the HapMap database show that the G allele is dominant in Asians, while the A allele is dominant in Caucasians and African Americans.…”

Section: Discussionsupporting

confidence: 92%

“…We have shown that both Japanese (15) and Japanese-Brazilian (20) subjects with the AA genotype have a reduced risk of gastric atrophy as compared to GG genotype carriers. This suggests that the AA genotype might be related to the formation of a less active form of SHP-2.…”

Section: Discussionmentioning

confidence: 85%

Modification of the effect of smoking on cholesterol in Japanese carriers of a PTPN11 polymorphism

Okada

Suzuki²,

Nishio

et al. 2008

Mol Med Report

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Abstract.A widely-expressed protein tyrosine phosphatase, SHP-2, regulates apoB secretion by insulin. We hypothesised that a variation in the SHP-2 gene, PTPN11, may interact with smoking to influence serum lipid concentrations. The study comprised 794 subjects (278 males and 516 females), aged 39-88 years, who attended a health examination in Hokkaido, Japan in 2003. Subjects were genotyped for a G/A PTPN11 polymorphism (rs2301756). The mean serum LDL cholesterol, HDL cholesterol and triglyceride levels, stratified by genotype, were compared between current and non-(never or ex-) smokers. Among the AA genotype carriers, LDL cholesterol levels were significantly decreased in current vs. nonsmokers [mean ± SD, 101±34 mg/dl vs. 146±40 mg/dl; b (adjusted mean difference) = -56.0; 95% CI -102.8 to -9.3; p=0.019 after adjustment for age, sex and body mass index]. In contrast, HDL cholesterol levels were increased in current vs. non-smokers (66±5 mg/dl vs. 58±12 mg/dl; b=14.9; 95% CI 3.1 to 26.8; p=0.014 after adjustment). The interaction between a current smoking habit and the AA genotype had a significant effect on LDL and HDL cholesterol (LDL-C, p=0.039; HDL-C, p=0.020). These data suggest that cigarette smoking might alter the metabolism of cholesterol in Japanese PTPN11 AA genotype carriers. IntroductionCigarette smoking and an increased level of LDL cholesterol (LDL-C) or decreased level of HDL cholesterol (HDL-C) are risk factors for cardiovascular disease. Increases in LDL-C levels and decreases in HDL-C levels have been observed in smokers (1), and a positive multiplicative interaction between smoking and LDL-C levels in coronary heart disease incidence has been observed (2). Cigarette smoking is an oxidative stress that causes genetic damage (3) and can either up-or downregulate gene expression levels (4). Studies have tried to clarify the effect of the gene-smoking interaction on lipid concentrations (5,6), and have revealed that both genetic variants and environmental factors, including a current smoking habit, influence serum cholesterol levels (7).Src homology 2 domain-containing protein tyrosine phosphatase-2 (SHP-2) is a widely-expressed protein tyrosine phosphatase (8) that regulates both acute and adaptive control of apoB secretion by insulin (9-11). The PTPN11 gene, which encodes SHP-2, is on chromosome 12 and contains 16 exons. Jamshidi et al selected three tagging single nucleotide polymorphisms (SNPs), rs11066322, rs11066320 and rs2301756, and demonstrated in a Caucasian female population that PTPN11 rs11066322 was associated with apoB levels and rs11066320 with LDL-C levels (12). However, the NCBI Variation Database shows that, in the Japanese population, SNP rs11066320 does not exist or is very rare, while rs11066322 and rs2301756 are in nearly complete linkage disequilibrium with each other. We therefore selected rs2301756, (IMS-JST057927 in the Japan Single Nucleotide Polymorphism database), located in intron 3, 223-bp upstream of exon 4, as a candidate SNP influencing LDL-C levels among the ...

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“…New sequencing technologies enable us to study organisms of larger genomes, including humans. Currently, genetic susceptibility factors of the human host are studied on the basis of individual genes (Correa, 2005; Kawai et al, 2006; Shanks and El-Omar, 2009), but the new technologies will enhance the identification of host genetic factors. Progress of studies on both human and microbe genomics will unveil conflicts and co-evolution between the host and the parasites.…”

Section: Impact Of Advanced Sequencing Technologymentioning

confidence: 99%

Molecular epidemiology, population genetics, and pathogenic role of Helicobacter pylori

Suzuki

Shiota

Yamaoka

2012

Infection, Genetics and Evolution

129

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Helicobacter pylori infection is linked to various gastroduodenal diseases; however, only approximately 20% of infected individuals develop severe diseases. Despite the high prevalence of H. pylori infection in Africa and South Asia, the incidence of gastric cancer in these areas is much lower than in other countries. Furthermore, the incidence of gastric cancer tends to decrease from north to south in East Asia. Such geographic differences in the pathology can be explained, at least in part, by the presence of different types of H. pylori virulence factors, especially cagA, vacA, and the right end of the cag pathogenicity island. The genotype of the virulence genes is also useful as a tool to track human migration utilizing the high genetic diversity and frequent recombination between different H. pylori strains. Multilocus sequence typing (MLST) analysis using 7 housekeeping genes can also help predict the history of human migrations. Population structure analysis based on MLST has revealed 7 modern population types of H. pylori, which derived from 6 ancestral populations. Interestingly, the incidence of gastric cancer is closely related to the distribution of H. pylori populations. The different incidence of gastric cancer can be partly attributed to the different genotypes of H. pylori circulating in different geographic areas. Although approaches by MLST and virulence factors are effective, these methods focus on a small number of genes and may miss information conveyed by the rest of the genome. Genome-wide analyses using DNA microarray or whole-genome sequencing technology give a broad view on the genome of H. pylori. In particular, next-generation sequencers, which can read DNA sequences in less time and at lower costs than Sanger sequencing, enabled us to efficiently investigate not only the evolution of H. pylori, but also novel virulence factors and genomic changes related to drug resistance.

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Significant association between PTPN11 polymorphism and gastric atrophy among Japanese Brazilians

Cited by 13 publications

References 37 publications

Associations of a PTPN11 G/A polymorphism at intron 3 with Helicobactor pyloriseropositivity, gastric atrophy and gastric cancer in Japanese

Associations of a PTPN11 G/A polymorphism at intron 3 with Helicobactor pyloriseropositivity, gastric atrophy and gastric cancer in Japanese

Modification of the effect of smoking on cholesterol in Japanese carriers of a PTPN11 polymorphism

Molecular epidemiology, population genetics, and pathogenic role of Helicobacter pylori

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