Variant in the 3' region of the IkappaBalpha gene associated with insulin resistance in Hispanic Americans: The IRAS Family Study.
Variant in the 3' region of the IkappaBalpha gene associated with insulin resistance in Hispanic Americans: The IRAS Family Study.
复制标题
DOI:
10.1038/oby.2009.303
复制
发表时间:
2010-03
期刊:
影响因子:
6.9
通讯作者:
Fingerlin, Tasha E.
中科院分区:
文献类型:
--
作者:
Miller, Melissa R.;Zhang, Weiming;Sibbel, Scott P.;Langefeld, Carl D.;Bowden, Donald W.;Haffner, Steven M.;Bergman, Richard N.;Norris, Jill M.;Fingerlin, Tasha E.
The IKKβ/NF-κB pathway is known to play an important role in inflammatory response and has also recently been implicated in the process of insulin resistance. We hypothesized that one or more variants in the IκBα gene (NFKBIA) or surrounding untranslated regions would be associated with insulin sensitivity (SI) in Hispanic-American families. We tested for association between 25 single-nucleotide polymorphisms (SNPs) in and near NFKBIA and SI in 981 individuals in 90 Hispanic-American families from the Insulin Resistance Atherosclerosis (IRAS) Family Study. SNP rs1951276 in the 3′ flanking region of NFKBIA was associated with SI in the San Antonio (SA) sample after adjusting for age, gender, and admixture (uncorrected P = 1.69 × 10−5; conservative Bonferroni correction P = 3.38 × 10−4). Subjects with at least one A allele for NFKBIA rs1951276 had ~29% lower SI compared to individuals homozygous for the G allele in the SA sample. Although not statistically significant, the effect was in the same direction in the San Luis Valley (SLV) sample alone (P = 0.348) and was significant in the combined SA and SLV samples (P = 5.37 × 10−4; presence of A allele associated with ~20% lower SI). In SA, when adjusted for subcutaneous adipose tissue area (SAT, cm2), the association was modestly attenuated (P = 1.25 × 10−3), but the association remained highly significant after adjustment for visceral adipose tissue area (VAT, cm2; P = 4.41 × 10−6). These results provide corroborating evidence that the NF-κB/IKKβ pathway may mediate obesity-induced insulin resistance in humans.
登录
查看更多内容
影响因子:
2.8
作者:
Klein, W;Tromm, A;Griga, T
通讯作者:
Griga, T
影响因子:
19.6
作者:
Festa, A;D'Agostino, R;Haffner, SM
通讯作者:
Haffner, SM
影响因子:
56.9
作者:
KOPP, E;GHOSH, S
通讯作者:
GHOSH, S
DOI:
10.1073/pnas.021506298
发表时间:
2001-01-16
影响因子:
11.1
作者:
Buetow, KH;Edmonson, M;Braun, A
通讯作者:
Braun, A
影响因子:
7.7
作者:
Rich, SS;Bowden, DW;Bergmans, RN
通讯作者:
Bergmans, RN