Assessment of established HDL-C loci for association with HDL-C levels and type 2 diabetes in Pima Indians.
Assessment of established HDL-C loci for association with HDL-C levels and type 2 diabetes in Pima Indians.
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DOI：
10.1007/s00125-015-3835-x
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发表时间：
2016-03
期刊：
影响因子：
8.2
通讯作者：
Baier LJ
中科院分区：
文献类型：
--
作者：
Nair AK;Piaggi P;McLean NA;Kaur M;Kobes S;Knowler WC;Bogardus C;Hanson RL;Baier LJ
皮马印第安人的流行病学研究发现，高水平的高密度脂蛋白胆固醇（HDL-C）是女性预防2型糖尿病风险的保护因素。我们评估了hdl - c相关的单核苷酸多态性（snp）是否也与女性皮马印第安人的2型糖尿病有关。在2,675名皮马印第安人的全遗产中，初步分析了已建立的HDL-C位点中的21个snp。在7710名皮马印第安人（55.6%为女性）中评估了与HDL-C相关的snp（12个snp）与2型糖尿病的相关性。CETP位点提供了与HDL-C相关的最有力证据，并通过分析标签snp进一步进行了研究。分析的21个snp中有12个与皮马印第安人的HDL-C显著相关；代表4个位点（CETP、DOCK6、PPP1R3B和ABCA1）的5个snp达到全基因组显著性。三个snp （CETP、KLF14和HNF4A）仅在具有降低hdl - c等位基因的女性参与者中与2型糖尿病相关，增加糖尿病风险（p值：3.2 × 10−4至7.7 × 10−5）；即使在调整HDL-C后，这种关联仍然显著。在CETP的其他分析中，发现rs6499863与女性2型糖尿病的相关性最强（p = 5.0 × 10−6），并且这种相关性与HDL-C的相关性保持独立。CETP、HNF4A和KLF14位点的snp与HDL-C水平和2型糖尿病相关（在女性参与者中）。然而，由于HNF4A和KLF14是2型糖尿病的既定基因座，因此HDL-C不太可能单独介导这些关联。
Epidemiological studies in Pima Indians identified elevated levels of HDL-cholesterol (HDL-C) as a protective factor against type 2 diabetes risk in women. We assessed whether HDL-C-associated single-nucleotide polymorphisms (SNPs) also associate with type 2 diabetes in female Pima Indians. Twenty-one SNPs in established HDL-C loci were initially analysed in 2,675 full-heritage Pima Indians. SNPs shown to associate with HDL-C (12 SNPs) were assessed for association with type 2 diabetes in 7,710 Pima Indians (55.6% female sex). The CETP locus provided the strongest evidence for association with HDL-C and was further interrogated by analysing tag SNPs. Twelve of the 21 SNPs analysed had a significant association with HDL-C in Pima Indians; five SNPs representing four loci (CETP, DOCK6, PPP1R3B and ABCA1) reached genome-wide significance. Three SNPs, at CETP, KLF14 and HNF4A, associated with type 2 diabetes only in female participants with the HDL-C-lowering allele increasing diabetes risk (p values: 3.2 × 10 −4 to 7.7 × 10 −5); the association remained significant even after adjustment for HDL-C. Additional analysis across CETP identified rs6499863 as having the strongest association with type 2 diabetes in female participants (p = 5.0 × 10 −6) and this association remained independent of the HDL-C association. SNPs at the CETP, HNF4A and KLF14 locus are associated with HDL-C levels and type 2 diabetes (in female participants). However, since HNF4A and KLF14 are established loci for type 2 diabetes, it is unlikely that HDL-C solely mediates these associations.