Common variants of inflammatory cytokine genes are associated with risk of nephropathy in type 2 diabetes among Asian Indians.
Common variants of inflammatory cytokine genes are associated with risk of nephropathy in type 2 diabetes among Asian Indians.
复制标题
DOI：
10.1371/journal.pone.0005168
复制
发表时间：
2009
期刊：
影响因子：
3.7
通讯作者：
Singal PK
中科院分区：
文献类型：
--
作者：
Ahluwalia TS;Khullar M;Ahuja M;Kohli HS;Bhansali A;Mohan V;Venkatesan R;Rai TS;Sud K;Singal PK
炎性细胞因子基因已被认为是糖尿病肾病易感性的良好候选基因。在本研究中，我们研究了促炎细胞因子基因的多个等位基因的联合作用，以确定2型糖尿病患者肾病的风险。在两个独立确定的2型糖尿病伴（DN）和不伴肾病（DM）队列中，对促炎性细胞因子基因（CCL 2、TGFB 1、IL 8、CCR 5和MMP 9）的8个单核苷酸多态性（SNP）进行基因分型，包括来自印度北部（n = 495）和印度南部（n = 188）的患者。 采用PCR、等位基因特异性引物PCR（ASO-PCR）、PCR-RFLP和TaqMan等位基因识别技术进行基因分型，采用MDR软件分析基因间的相互作用。ELISA法检测血清超敏C反应蛋白（hs-CRP）水平。DN组hs-CRP水平明显高于DM组（P<0.05）。CCL 2、IL 8、CCR 5和MMP 9基因多态性与糖尿病肾病的发病风险相关。DN组CCL 2 II、IL 8 - 251 AA、CCR 5 59029 AA和MMP 9 279 Gln/Gln基因型频率显著高于DM组（p<0.05），并且与北印度和南印度队列中肾病风险增加相关。CCR 5 DD和IL 8 - 251 AA基因型仅在北印度DN组中更常见。在2型糖尿病患者中，风险相关基因型（II、-2518GG（CCL 2）、DD（CCR 5）和279 Gln/Gln（MMP 9））的共同出现使肾病风险增加10倍（p<0.0002）。本研究强调了炎症细胞因子基因的常见变异对DN的风险产生了适度的影响，并且风险等位基因的组合使亚洲印度人2型糖尿病肾病的风险大幅增加。
Inflammatory cytokine genes have been proposed as good candidate genes for conferring susceptibility to diabetic nephropathy. In the present study, we examined the combined effect of multiple alleles of pro inflammatory cytokine genes for determining the risk of nephropathy in type 2 diabetic patients. Eight single nucleotide polymorphisms (SNPs) of pro-inflammatory cytokine genes (CCL2, TGFB1, IL8, CCR5, and MMP9) were genotyped in two independently ascertained type 2 diabetic cohorts with (DN) and without nephropathy (DM); consisting of patients from North India (n = 495) and South India (n = 188). Genotyping was carried out using PCR, allele specific oligonucleotide-PCR (ASO-PCR), PCR-RFLP and TaqMan allelic discrimination assays and the gene–gene interaction among genetic variants were determined by multi dimensional reduction (MDR) software. Serum high sensitive CRP (hs-CRP) levels were measured by ELISA. The hs-CRP levels were significantly higher in DN as compared to the DM group (p<0.05). The CCL2, IL8, CCR5 and MMP9 polymorphisms were found to be associated with the risk of diabetic nephropathy. Frequency of CCL2 II, IL8 -251AA, CCR5 59029AA and MMP9 279Gln/Gln genotypes were significantly higher in DN than in DM group (p<0.05) and associated with an increased risk of nephropathy in both North and South Indian cohorts. CCR5 DD and IL8 -251AA genotypes were more prevalent in North Indian DN group only. The co-occurrence of risk associated genotypes (II, -2518GG (CCL2), DD (CCR5) and 279Gln/Gln (MMP9) conferred a tenfold increased risk of nephropathy among type 2 diabetics (p<0.0002). The present study highlights that common variants of inflammatory cytokine genes exert a modest effect on risk of DN and a combination of risk alleles confer a substantial increased risk of nephropathy in type 2 diabetes among Asian Indians.
登录
查看更多内容
影响因子：
7
作者：
Basu, A;Mukherjee, N;Majumder, PP
通讯作者：
Majumder, PP
影响因子：
168.9
作者：
Hattersley, AT;McCarthy, MI
通讯作者：
McCarthy, MI
影响因子：
3.1
作者：
Ahluwalia, Tarunveer Singh;Ahuja, Monica;Khullar, Madhu
通讯作者：
Khullar, Madhu
影响因子：
2.5
作者：
Lee, SH;Lee, TW;Chung, JH
通讯作者：
Chung, JH
影响因子：
5.8
作者：
Hahn, LW;Ritchie, MD;Moore, JH
通讯作者：
Moore, JH