Genetic Susceptibility for Coronary Heart Disease and Type 2 Diabetes Complications

[摘要] Type II diabetes (T2D)3 represents a major public health challenge, with the WHO having estimated a current prevalence of 346 million worldwide. Cardiovascular disease, including coronary heart disease (CHD), stroke, and peripheral vascular disease, is one of the major complications of T2D, and the development of new strategies to tackle this problem is undoubtedly necessary. Although the association between diabetes and cardiovascular risk is well established, the pathologic basis of CHD in patients with T2D may differ from that in the general population. Whether this relationship has a genetic component is not fully understood.With regard to understanding the genetic basis of complex diseases, genomewide association studies (GWASs) have led to an unprecedented number of well-validated variants associated with complex diseases. There is now considerable interest in understanding both the mechanism by which these variants confer risk and whether the variants identified will be useful for predicting complex disease phenotypes.A recent report by Qi et al. (1) addressed 2 questions in this regard: ( a ) Are single-nucleotide polymorphisms (SNPs) identified by GWASs of CHD associated with the risk of CHD in T2D, and ( b ) can these variants be combined in a score that will aid prediction of CHD risk in T2D? In investigating these questions, Qi and coworkers genotyped 12 CHD susceptibility loci in 3 nested case–control studies of CHD in T2D: the Nurses' Health Study, the Health Professional Follow-Up Study, and the Joslin Heart Study.As expected, the chromosome 9p21 CHD risk locus showed a strong association with CHD risk, whereas 4 other loci [ PHACTR1 4 (phosphatase and actin regulator 1), HNF1A (HNF1 homeobox A), PCSK9 (proprotein convertase subtilisin/kexin type 9), and SORT1 (sortilin 1)] demonstrated associations consistent with those seen in previous GWAS reports, with P values <0.05. Interestingly, haplotypes associated with increased CHD risk and …

[学科分类] 过敏症与临床免疫学