Trends in high-risk HLA susceptibility genes among Colorado youth with type 1 diabetes.
Trends in high-risk HLA susceptibility genes among Colorado youth with type 1 diabetes.
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DOI：
10.2337/dc07-2210
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发表时间：
2008-07
期刊：
影响因子：
16.2
通讯作者：
Dabelea D
中科院分区：
文献类型：
--
作者：
Vehik K;Hamman RF;Lezotte D;Norris JM;Klingensmith GJ;Rewers M;Dabelea D
1型糖尿病与HLA II类系统内的广谱易感性和保护性基因型相关。据报道，最近被诊断患有青年发病的1型糖尿病的成年人被发现比几十年前诊断的人具有更少的经典高危HLA II类基因型。我们假设在1978年至2004年在科罗拉多被诊断为1型糖尿病的5- 17岁西班牙裔和非西班牙裔白色（NHW）青年中，HLA-DR、DQ基因型分布的这种时间趋势是明显的，甚至可能更强。研究设计和方法：采用PCR和序列特异性寡核苷酸杂交对1978-1988年诊断的100名青年和2002-2004年诊断的264名青年进行HLA-DR、DQ分型。Logistic回归用于调整混杂因素并评估时间趋势。在1978-1988年诊断的儿童中，最高风险基因型（DRB 1 *03-DQB 1 *02/DRB 1 *04-DQB 1 *03）的频率（39%）高于2002-2004年诊断的儿童（28%）。在NHWs和西班牙裔中观察到类似的模式。结论：我们发现，随着时间的推移，高危HLA基因型在NHW和西班牙裔青年1型糖尿病患者中越来越少。这种时间趋势可能表明，增加环境暴露现在能够在遗传易感性较低的受试者中引发1型糖尿病。
OBJECTIVE—Type 1 diabetes is associated with a wide spectrum of susceptibility and protective genotypes within the HLA class II system. It has been reported that adults diagnosed with youth-onset type 1 diabetes more recently have been found to have fewer classical high-risk HLA class II genotypes than those diagnosed several decades ago. We hypothesized that such temporal trends in the distribution of HLA-DR, DQ genotypes would be evident, and perhaps even stronger, among 5- to 17-year-old Hispanic and non-Hispanic white (NHW) youth diagnosed with type 1 diabetes in Colorado between 1978 and 2004. RESEARCH DESIGN AND METHODS—HLA-DR, DQ was typed using PCR and sequence-specific oligonucleotide hybridization in 100 youth diagnosed during the period of 1978–1988 and 264 diagnosed during 2002–2004. Logistic regression was used to adjust for confounders and assess temporal trends. RESULTS—The frequency of the highest-risk genotype (DRB1*03-DQB1*02/DRB1*04-DQB1*03) was higher (39%) in children diagnosed during the period 1978–1988 than in those diagnosed during 2002–2004 (28%). A similar pattern was observed in NHWs and Hispanics. CONCLUSIONS—We found that high-risk HLA genotypes are becoming less frequent over time in youth with type 1 diabetes of NHW and Hispanic origin. This temporal trend may suggest that increasing environmental exposure is now able to trigger type 1 diabetes in subjects who are less genetically susceptible.
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影响因子：
8.2
作者：
Gale, EAM
通讯作者：
Gale, EAM
影响因子：
16.2
作者：
Vehik, Kendra;Hamman, Richard F.;Dabelea, Dana
通讯作者：
Dabelea, Dana
影响因子：
8.2
作者：
Hermann, R;Knip, M;Ilonen, J
通讯作者：
Ilonen, J
影响因子：
16.2
作者：
CRUICKSHANKS, KJ;JOBIM, LF;HAMMAN, RF
通讯作者：
HAMMAN, RF
DOI：
10.1016/j.cct.2004.08.002
发表时间：
2004-10-01
期刊：
CONTROLLED CLINICAL TRIALS
影响因子：
--
作者：
Pettitt, DJ;Bell, R;Williams, D
通讯作者：
Williams, D