Petrone A, Battelino T, Krzisnik C, Bugawan T, Erlich H, Di Mario U, Pozzilli P, Buzzetti R
Endocrinologia, Dipartimento di Scienze Cliniche, University La Sapienza, Rome, Italy.
Tissue Antigens. 2002 Sep;60(3):244-53. doi: 10.1034/j.1399-0039.2002.600306.x.
The incidence of type 1 diabetes (T1DM) seems to depend in part on the population frequencies of susceptible and protective HLA haplotypes. The present study aimed to (i): characterize the genetic susceptibility to T1DM in the Slovenian population, (ii) test the general hypothesis that T1DM incidence is related to the frequencies of susceptible/protective haplotypes, (iii) compare allele, haplotype and genotype frequencies in Slovenians and Italians that represent two white populations with a similar incidence of T1DM (7.9/100,000/year and 8.1/100,000/year, respectively). The haplotype found most frequently among Slovenian T1DM patients was DRB10301-DQA10501-DQB10201 (53%). The DR4-DQA10301-DQB10302 haplotypes conferring susceptibility to T1DM were those bearing DRB10401 (OR = 12), DRB10404 (OR = 4.7) and DRB10402 (OR = 4.5). Negative associations with the disease were found for the following haplotypes: DRB11501-DQA10102-DQB10602, DRB11301-DQA10102-DQB10603, DRB11101/1104-DQA10501-DQB10301, and DRB11401-DQA10101-DQB10503. Our findings indicate that the low frequencies of susceptible genotypes, in particular, DR3-DQA10501-DQB10201/DR4-DQA10301-DQB10302, together with a high frequency of protective haplotypes, could in part explain the low incidence of T1DM in the Slovenian population. The combined frequencies of susceptible genotypes were similar in the two populations (Slovenia = 19.2%, Italy = 17.6%), and the 95% confidence limits of the OR values for each genotype in the two populations overlapped, indicating no significant differences between the values. We conclude that the similar incidences of T1DM in Italian and Slovenian populations are in part a reflection of similar frequencies of HLA susceptible/protective haplotypes.
1型糖尿病（T1DM）的发病率似乎部分取决于易感和保护性HLA单倍型的人群频率。本研究旨在：（i）描述斯洛文尼亚人群中T1DM的遗传易感性；（ii）检验T1DM发病率与易感/保护性单倍型频率相关的一般假设；（iii）比较斯洛文尼亚人和意大利人（代表两个T1DM发病率相似的白种人群，分别为7.9/100,000/年和8.1/100,000/年）的等位基因、单倍型和基因型频率。在斯洛文尼亚T1DM患者中最常发现的单倍型是DRB10301 - DQA10501 - DQB10201（53%）。赋予T1DM易感性的DR4 - DQA10301 - DQB10302单倍型是携带DRB10401（比值比[OR]=12）、DRB10404（OR = 4.7）和DRB10402（OR = 4.5）的单倍型。发现以下单倍型与该疾病呈负相关：DRB11501 - DQA!0102 - DQB10602、DRB11301 - DQA10102 - DQB10603、DRB11101/1104 - DQA10501 - DQB10301和DRB11401 - DQA10101 - DQB10503。我们的研究结果表明，易感基因型频率较低，特别是DR3 - DQA10501 - DQB10201/DR4 - DQA10301 - DQB10302，以及保护性单倍型频率较高，可能部分解释了斯洛文尼亚人群中T1DM发病率较低的原因。两个群体中易感基因型的合并频率相似（斯洛文尼亚=19.2%，意大利=17.6%），并且两个群体中每种基因型的OR值的95%置信区间重叠，表明这些值之间没有显著差异。我们得出结论，意大利和斯洛文尼亚人群中T1DM发病率相似，部分反映了HLA易感/保护性单倍型频率相似。
