Shaat N, Karlsson E, Lernmark A, Ivarsson S, Lynch K, Parikh H, Almgren P, Berntorp K, Groop L
Department of Clinical Sciences/Diabetes and Endocrinology, Malmö University Hospital, Lund University, Malmö, Sweden.
Diabetologia. 2006 Jul;49(7):1545-51. doi: 10.1007/s00125-006-0258-8. Epub 2006 Apr 26.
AIMS/HYPOTHESIS: Impaired beta cell function is the hallmark of gestational diabetes mellitus (GDM) and MODY. In addition, women with MODY gene mutations often present with GDM, but it is not known whether common variants in MODY genes contribute to GDM.
We genotyped five common variants in the glucokinase (GCK, commonly known as MODY2), hepatocyte nuclear factor 1-alpha (HNF1A, commonly known as MODY3) and 4-alpha (HNF4A commonly known as MODY1) genes in 1,880 Scandinavian women (648 women with GDM and 1,232 pregnant non-diabetic control women).
The A allele of the GCK -30G-->A polymorphism was more common in GDM women than in control subjects (odds ratio [OR] 1.28 [95% CI 1.06-1.53], p=0.008, corrected p value, p=0.035). Under a recessive model [AA vs GA+GG], the OR increased further to 2.12 (95% CI 1.21-3.72, p=0.009). The frequency of the L allele of the HNF1A I27L polymorphism was slightly higher in GDM than in controls (1.16 [95% CI 1.001-1.34], p=0.048, corrected p value, p=0.17). However, the OR increased under a dominant model (LL+IL vs II; 1.31 [95% CI 1.08-1.60], p=0.007). The rs2144908, rs2425637 and rs1885088 variants, which are located downstream of the primary beta cell promoter (P2) of HNF4A, were not associated with GDM.
CONCLUSIONS/INTERPRETATION: The -30G-->A polymorphism of the beta-cell-specific promoter of GCK and the I27L polymorphism of HNF1A seem to increase the risk of GDM in Scandinavian women.
目的/假设：β细胞功能受损是妊娠期糖尿病（GDM）和青少年发病的成年型糖尿病（MODY）的标志。此外，携带MODY基因突变的女性常患GDM，但尚不清楚MODY基因的常见变异是否会导致GDM。
我们对1880名斯堪的纳维亚女性（648名GDM女性和1232名非糖尿病孕妇对照）的葡萄糖激酶（GCK，通常称为MODY2）、肝细胞核因子1α（HNF1A，通常称为MODY3）和4α（HNF4A，通常称为MODY1）基因中的五个常见变异进行了基因分型。
GCK -30G→A多态性的A等位基因在GDM女性中比在对照受试者中更常见（优势比[OR] 1.28 [95%可信区间1.06 - 1.53]，p = 0.008，校正p值，p = 0.035）。在隐性模型[AA与GA + GG]下，OR进一步增加至2.12（95%可信区间1.21 - 3.72，p = 0.009）。HNF1A I27L多态性的L等位基因频率在GDM中略高于对照（1.16 [95%可信区间1.001 - 1.34]，p = 0.048，校正p值，p = 0.17）。然而，在显性模型（LL + IL与II；1.31 [95%可信区间1.08 - 1.60]，p = 0.007）下OR增加。位于HNF4A主要β细胞启动子（P2）下游的rs2144908、rs2425637和rs1885088变异与GDM无关。
结论/解读：GCK的β细胞特异性启动子的 -30G→A多态性和HNF1A的I27L多态性似乎会增加斯堪的纳维亚女性患GDM的风险。
