Genetic polymorphisms in PTPN22, PADI-4, and CTLA-4 and risk for rheumatoid arthritis in two longitudinal cohort studies: evidence of gene-environment interactions with heavy cigarette smoking.
Genetic polymorphisms in PTPN22, PADI-4, and CTLA-4 and risk for rheumatoid arthritis in two longitudinal cohort studies: evidence of gene-environment interactions with heavy cigarette smoking.
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DOI：
10.1186/ar2421
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发表时间：
2008
影响因子：
4.9
通讯作者：
Karlson EW
中科院分区：
文献类型：
--
作者：
Costenbader KH;Chang SC;De Vivo I;Plenge R;Karlson EW
PTPN22，PADI-4和CTLA-4与类风湿关节炎的风险有关（RA）。与吸烟的互动。
我们研究了与PTPN22（RS2476601），PADI-4（RS2240340）和CTLA-4（RS3087243）相关的RA风险。在1989年，NHSII的年龄为25至42岁。对照设计涉及有遗传分析样本的参与者（NHS的45％和25％的NHSII），每个事件RA病例都与参与者相匹配，而没有RA出生，绝经后状态和绝经后激素的使用在ABI 7900 HT上使用Taqman单核苷酸多态性歧视（Applied Biosystems，850 Lincoln Center Drive，林肯中心驱动器，加利福尼亚州福斯特市，美国加利福尼亚州94404），并发表了人类白细胞抗原抗原抗原共享表位（HLA-SE-SE）基因型。我们采用了有条件的逻辑回归分析，调整了吸烟和生殖因素。
总共有437例RA病例与健康的女性对照组相匹配。 PTPN22的侵蚀与RA风险增加有关（多变量的主导模型= 1.46，95％的置信区间[CI] = 1.02至2.08）。观察到PTPN22与吸烟之间的显着乘法相互作用，观察到10个以上的包装年度（P = 0.04）。 1.27 [95％CI = 0.88至1.84]对于PADI-4的CTLA-4和1.04 [95％CI = 0.77至1.40]。
调整吸烟和生殖因子后，PTPN22与这些同龄人中的白种人妇女的RA风险有关。
PTPN22, PADI-4, and CTLA-4 have been associated with risk for rheumatoid arthritis (RA). We investigated whether polymorphisms in these genes were associated with RA in Caucasian women included in two large prospective cohorts, adjusting for confounding factors and testing for interactions with smoking. We studied RA risk associated with PTPN22 (rs2476601), PADI-4 (rs2240340), and CTLA-4 (rs3087243) in the Nurses' Health Study (NHS) and NHSII. Participants in NHS were aged 30 to 55 years at entry in 1976; those in NHSII were aged 25 to 42 years at entry in 1989. We confirmed incident RA cases through to 2002 in NHS and to 2003 in NHSII by questionnaire and medical record review. We excluded reports not confirmed as RA. In a nested case-control design involving participants for whom there were samples for genetic analyses (45% of NHS and 25% of NHSII), each incident RA case was matched to a participant without RA by year of birth, menopausal status, and postmenopausal hormone use. Genotyping was performed using Taqman single nucleotide polymorphism allelic discrimination on the ABI 7900 HT (Applied Biosystems, 850 Lincoln Centre Drive, Foster City, CA 94404 USA) with published primers. Human leukocyte antigen shared epitope (HLA-SE) genotyping was performed at high resolution. We employed conditional logistic regression analyses, adjusting for smoking and reproductive factors. We tested for additive and multiplicative interactions between each genotype and smoking. A total of 437 incident RA cases were matched to healthy female control individuals. Mean (± standard deviation) age at RA diagnosis was 55 (± 10), 57% of RA cases were rheumatoid factor (RF) positive, and 31% had radiographic erosions at diagnosis. PTPN22 was associated with increased RA risk (pooled odds ratio in multivariable dominant model = 1.46, 95% confidence interval [CI] = 1.02 to 2.08). The risk was stronger for RF-positive than for RF-negative RA. A significant multiplicative interaction between PTPN22 and smoking for more than 10 pack-years was observed (P = 0.04). CTLA-4 and PADI-4 genotypes were not associated with RA risk in the pooled results (pooled odds ratios in multivariable dominant models: 1.27 [95% CI = 0.88 to 1.84] for CTLA-4 and 1.04 [95% CI = 0.77 to 1.40] for PADI-4). No gene-gene interaction was observed between PTPN22 and HLA-SE. After adjusting for smoking and reproductive factors, PTPN22 was associated with RA risk among Caucasian women in these cohorts. We found both additive and multiplicative interactions between PTPN22 and heavy cigarette smoking.
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影响因子：
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Satten, Glen A.
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Ahlbom, A
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HERNANDEZAVILA, M;LIANG, MH;SPEIZER, FE
通讯作者：
SPEIZER, FE
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作者：
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