Department of Renal Medicine, Singapore General Hospital, Outram Road, Singapore 169608.
Singapore Med J. 2011 Nov;52(11):824-34.
Association studies with single nucleotide polymorphisms (SNPs) have been contradictory. Haplotypes may be more helpful. With gene sequencing, all SNPs can be found for construction of haplotypes.
The ACE gene was sequenced in four healthy Chinese subjects and 20 patients with IgA nephropathy (IgAN) to observe if differences exist among SNPs and haplotypes. 20 patients on angiotensin 1-converting enzyme inhibitor/angiotensin receptor antagonist (ACEI/ATRA) therapy were then compared with another 20 patients not treated with ACEI /ATRA to determine their renal outcome in response to ACEI/ATRA therapy and whether their genetic profile of ACE gene could play a role in determining their outcome to ACEI /ATRA therapy and progression to end-stage renal failure (ESRF).
IgAN patients had 53 variants, of which 17 were unique, whereas normal subjects had 38 variants, of which two were unique (p less than 0.005). No unique variant was a significant risk factor for IgAN. Significant genotype and allele frequency differences in five variants were observed between IgAN patients with renal impairment and those with ESRF (p less than 0.02).
Our data suggests that at least in the ACE gene, haplotyping SNPs within a single gene seems to have no added advantage over genotyping the individual component SNPs. The D allele and haplotype 3 confer an adverse prognosis, while the I allele and haplotype 5 appear to be renoprotective. The data suggests that genotypes of the ACE gene are linked to certain haplotypes, which could influence IgAN patients' response to ACEI/ATRA therapy.
与单核苷酸多态性（SNP）的关联研究一直存在争议。单体型可能更有帮助。通过基因测序，可以找到所有的 SNP 来构建单体型。
对 4 名健康中国受试者和 20 名 IgA 肾病（IgAN）患者的 ACE 基因进行测序，观察 SNP 和单体型之间是否存在差异。然后将 20 名接受血管紧张素 1 转换酶抑制剂/血管紧张素受体拮抗剂（ACEI/ATRA）治疗的患者与另外 20 名未接受 ACEI/ATRA 治疗的患者进行比较，以确定他们对 ACEI/ATRA 治疗的肾脏预后，以及他们的 ACE 基因遗传特征是否在决定他们对 ACEI/ATRA 治疗的反应和进展至终末期肾衰竭（ESRF）方面发挥作用。
IgAN 患者有 53 种变体，其中 17 种是独特的，而正常受试者有 38 种变体，其中两种是独特的（p 小于 0.005）。没有独特的变异是 IgAN 的显著危险因素。在肾功能不全和 ESRF 的 IgAN 患者之间观察到五个变体的显著基因型和等位基因频率差异（p 小于 0.02）。
我们的数据表明，至少在 ACE 基因中，在单个基因内对 SNP 进行单体型分析似乎没有比对个体 SNP 进行基因分型更有优势。D 等位基因和单体型 3 预示着不良预后，而 I 等位基因和单体型 5 似乎具有肾保护作用。数据表明，ACE 基因的基因型与某些单体型相关，这可能影响 IgAN 患者对 ACEI/ATRA 治疗的反应。
