Małecki Maciej T, Klupa Tomasz, Waluś Małgorzata, Czogała Wojciech, Greenlaw Paul, Sieradzki Jacek
Department of Metabolic Diseases, Medical College, Jagellonian University, Cracow, Poland.
Med Sci Monit. 2003 Feb;9(2):BR91-5.
Hereditary hemochromatosis (HH) is characterized by excess iron deposition. Two mutations in the HFE gene are associated with HH. Heterozygous carriers of HFE mutations are at higher risk of developing type 2 diabetes mellitus (T2DM). The aims of our project were to identify the frequency of C282Y and H63D mutations in a population from the Małopolska region of south-eastern Poland, and to search for an association of HFE mutations with T2DM.
MATERIAL/METHODS: We included 391 individuals in this study: 222 T2DM patients and 169 controls. Genotypes were determined by electrophoresis of the DNA digestion products from SnaBI and DpnII, respectively. Differences in distributions between the groups were then analyzed by the chi-squared test.
The frequency of wild/C282Y alleles was 98.2%/1.8% in T2DM patients and 96.7%/3.2% in controls (p=0.19). The frequency of wild/H63D alleles was 85.6%/14.4% and 88.8%/11.2% (p= 0.19), respectively. The distribution of genotypes was not statistically different. However, in stratified analyses based on age of T2DM onset and gender, we observed a higher prevalence of wild/H63D and H63D/H63D genotypes among T2DM patients diagnosed at > 49 years of age, the mean age for the entire group (p=0.018), and among male T2DM individuals (p=0.005) than in controls.
The frequency of HH-associated mutations in this population from south-eastern Poland is similar to other Caucasians. We found no evidence for the association of the C282Y mutation with T2DM. The results do suggest, however, that the H63D mutation may play a role in the pathogenesis of late onset T2DM and in males in this Polish population.
遗传性血色素沉着症（HH）的特征是铁过度沉积。HFE基因的两种突变与HH相关。HFE突变的杂合携带者患2型糖尿病（T2DM）的风险更高。我们项目的目的是确定波兰东南部小波兰地区人群中C282Y和H63D突变的频率，并寻找HFE突变与T2DM之间的关联。
材料/方法：我们纳入了391名个体进行本研究：222名T2DM患者和169名对照。分别通过对来自SnaBI和DpnII的DNA消化产物进行电泳来确定基因型。然后通过卡方检验分析两组之间分布的差异。
T2DM患者中野生型/C282Y等位基因的频率为98.2%/1.8%，对照中为96.7%/3.2%（p = 0.19）。野生型/H63D等位基因的频率分别为85.6%/14.4%和88.8%/11.2%（p = 0.19）。基因型分布无统计学差异。然而，在基于T2DM发病年龄和性别的分层分析中，我们观察到在诊断时年龄>49岁（整个组的平均年龄）的T2DM患者中以及男性T2DM个体中，野生型/H63D和H63D/H63D基因型的患病率高于对照（p = 0.018和p = 0.005）。
波兰东南部该人群中与HH相关的突变频率与其他白种人相似。我们没有发现C282Y突变与T2DM相关的证据。然而，结果确实表明H63D突变可能在波兰人群中晚发性T2DM的发病机制中以及男性中起作用。
