与HLA DQB1基因相邻的逆转录病毒长末端重复序列（DQ-LTR13）改变了高风险DQ单倍型上的I型糖尿病易感性。
A retroviral long terminal repeat adjacent to the HLA DQB1 gene (DQ-LTR13) modifies Type I diabetes susceptibility on high risk DQ haplotypes.
作者信息
Bieda K, Pani M A, van der Auwera B, Seidl C, Tönjes R R, Gorus F, Usadel K H, Badenhoop K
机构信息
Department of Medicine I, Division of Endocrinology, University Hospital Frankfurt am Main, Germany.
出版信息
Diabetologia. 2002 Mar;45(3):443-7. doi: 10.1007/s00125-001-0753-x.
AIMS/HYPOTHESIS: HLA-DQ genes, located in the human leukocyte antigen region on chromosome 6 p, are the main inherited factors predisposing to Type I (insulin-dependent) diabetes mellitus. Endogenous retroviral long-terminal repeats are integrated at several sites within this region, one of which is known to enhance susceptibility for Type I diabetes. We examined another LTR within the HLA-region as an additional genetic risk marker.
METHODS
We investigated the segregation of one long-terminal repeat (DQ-LTR13), located 1.3 kb upstream of HLA DQB1 with different HLA-DQ haplotypes, and its transmission to patients. A total of 284 Caucasian families (203 German and 81 Belgian) with at least one diabetic offspring were genotyped for DQA1, DQB1 and DQ-LTR13.
RESULTS
DQ8/LTR13(+) was preferentially transmitted (139 transmitted vs 28 not transmitted; P(TDT) = 1.67 x 10(-14)) whereas no deviation from expected transmission frequencies was observed for DQ8/LTR13(-) (20 transmitted vs 17 not transmitted; P(TDT) = 1.00). DQ8/LTR13(+) alleles conferred a significantly higher risk for Type I diabetes than DQ8/LTR13(-) alleles (p chi(2) = 2.58 x 10(-14)). This difference remained significant even after DRB1 subtyping (p chi(2) = 0.02). Also, there was a significant difference when comparing the transmission of DQ2/LTR13(+) and DQ2/LTR13(-) alleles (p chi(2) = 0.01), the latter conferring an increased risk. The transmission of DQ-LTR13(+) haplotypes did not show any differences regarding paternal, maternal or gender-related stratification. However, DQ8/LTR13(-) was significantly more often transmitted from mothers (p chi(2) = 0.01) and to female patients (p chi(2) = 0.04).
CONCLUSION/INTERPRETATION: We conclude that DQ-LTR13 marks additional genetic risk for Type I diabetes on predisposing DRB1(*)0401- DQ8 and DQ2 haplotypes and will help to further define susceptibility in this gene region.
目的/假设：位于6号染色体短臂上人类白细胞抗原区域的HLA - DQ基因是I型（胰岛素依赖型）糖尿病的主要遗传易患因素。内源性逆转录病毒长末端重复序列整合在该区域的多个位点，其中一个位点已知会增加I型糖尿病的易感性。我们研究了HLA区域内的另一个长末端重复序列作为额外的遗传风险标志物。
方法
我们研究了位于HLA DQB1上游1.3 kb处的一个长末端重复序列（DQ - LTR13）与不同HLA - DQ单倍型的分离情况及其向患者的传递。对总共284个至少有一个糖尿病后代的白种人家庭（203个德国家庭和81个比利时家庭）进行了DQA1、DQB1和DQ - LTR13基因分型。
结果
DQ8/LTR13(+)被优先传递（传递139次，未传递28次；P(TDT) = 1.67×10⁻¹⁴），而DQ8/LTR13(-)未观察到与预期传递频率的偏差（传递20次，未传递17次；P(TDT) = 1.00）。DQ8/LTR13(+)等位基因比DQ8/LTR13(-)等位基因赋予I型糖尿病显著更高的风险（p卡方 = 2.58×10⁻¹⁴）。即使在DRB1亚型分型后，这种差异仍然显著（p卡方 = 0.02）。此外，比较DQ2/LTR13(+)和DQ2/LTR13(-)等位基因的传递时也存在显著差异（p卡方 = 0.01），后者赋予更高的风险。DQ - LTR13(+)单倍型的传递在父系、母系或性别相关分层方面没有显示出任何差异。然而，DQ8/LTR13(-)从母亲传递的频率显著更高（p卡方 = 0.01），并且传递给女性患者的频率也更高（p卡方 = 0.04）。
结论/解读：我们得出结论，DQ - LTR13标记了I型糖尿病在易患DRB1(*)0401 - DQ8和DQ2单倍型上的额外遗传风险，并将有助于进一步确定该基因区域的易感性。
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