糖尿病基因的探討: 從多基因到多校基因

Objective Diabetic nephropathy (DN) and diabetic retinopathy (DR) comprise major microvascular complications of diabetes that occur with a high concordance rate in patients and are considered to potentially share pathogeneses. In this case-control study, we sought to investigate whether DR-related single nucleotide polymorphisms (SNPs) exert pleiotropic effects on renal function outcomes among patients with diabetes.

Research Design and Methods A total of 33 DR-related SNPs were identified by replicating published SNPs and via a genome wide association study. Furthermore, we assessed the cumulative effects by creating a weighted genetic risk score and evaluated the discriminatory and prediction ability of these genetic variants using DN cases according to estimated glomerular filtration rate (eGFR) status along with a cohort with early renal functional decline (ERFD).

Results Multivariate logistic regression models revealed that the DR-related SNPs afforded no individual or cumulative genetic effect on the nephropathy risk, eGFR status, or ERFD outcome among patients with type 2 diabetes in Taiwan.

Conclusion Our findings indicate that larger studies would be necessary to clearly ascertain the effects of individual genetic variants and further investigation is also required to identify other genetic pathways underlying DN.

 

在糖尿病病人中,腎病變(diabetic nephropathy)與視網膜病變(diabetic retinopathy, DR)是兩種常見的糖尿病微小血管併發症,有較高一致性的發生,並可能共享致病機制。而具有多效作用(pleiotropic effects)的遺傳基因,就可能是DNDR表型關聯之基礎。在本研究中我們探討與DR相關的單核苷酸多態性(SNP)是否對糖尿病患者的腎功能及其功能衰退產生多效性作用。

    我們利用全基因組關聯研究及針對已發表的SNP進行驗證,在台灣第二型糖尿病患者中,共鑑定出33個與DR相關的SNPs,並建加權基因風險分數(genetic risk score, GRS)來評估累積效應。進一步利用具有不同腎小球濾過率(eGFR)狀態及發生早期腎功能衰退(early renal function decline, ERFD)的兩組病例對照組,評估這些與DR相關SNPs對於腎功能的影響。透過多元邏輯斯回歸模型分析,結果顯示,DR相關SNPs對腎病風險,包含eGFR狀況或ERFD,沒有單獨或累積的遺傳效應。結論,對於基因多效作用於不同糖尿病併發症的影響需進行更大的研究來釐清,並且對DN其他遺傳途徑做持續的探索。