近日,，國家交叉中心李啟寨副研究員與美國國家癌癥研究所的科研人員合作,，在25羥基維他命D循環(huán)水平的全基因組關(guān)聯(lián)分析取得階段性成果。該成果發(fā)表在《人類分子遺傳學(xué)》期刊,。
羥基維他命循環(huán)水平的全基因組關(guān)聯(lián)分析
他們對2396個病例和2105個對照的基因組上的593253個突變位點(diǎn)進(jìn)行了25羥基維他命D循環(huán)水平的關(guān)聯(lián)分析,，統(tǒng)計分析結(jié)果如圖1所示。他們發(fā)現(xiàn)位于4號染色體的突變位點(diǎn)rs22582679與25羥基維他命D的循環(huán)水平有關(guān)聯(lián) (p-value=2×10-30); 而且他們還發(fā)現(xiàn)另外三個突變位點(diǎn): rs3829251 (p-value=8.8×10-7),，rs6599638 (p-value=3.3×10-7),，rs2060793 (p-value=1.4×10-5)也有可能與25羥基維他命D的循環(huán)水平也有關(guān)聯(lián)。
此前,，基于雙胞胎數(shù)據(jù),，研究者們發(fā)現(xiàn)了與維他命D的循環(huán)水平相關(guān)聯(lián)的遺傳因素，但是由于數(shù)據(jù)量少,，沒有得出確定性的結(jié)論,。而李啟寨副研究員的這一研究結(jié)果將為人們開發(fā)有效藥物治療與25羥基維他命D相關(guān)的疾病提供靶點(diǎn)。
維他命D的功能非常多,，它能調(diào)節(jié)人體內(nèi)的鈣平衡,，促進(jìn)鈣和磷的吸收代謝，促進(jìn)細(xì)胞正常生長,，增強(qiáng)免疫系統(tǒng),，保持荷爾蒙平衡等。維他命D在人體內(nèi)的主要循環(huán)形式的25羥基維他命D[25(OH)D]與人類的許多復(fù)雜疾病相關(guān),，比如,，佝僂病、骨質(zhì)疏松癥和多發(fā)性硬化癥等,。維他命D的受體響應(yīng)元直接或間接地影響細(xì)胞周期和增殖，分化和凋亡,。與維他命D關(guān)聯(lián)的常見遺傳變異可能是科學(xué)家們識別維他命D缺乏風(fēng)險的重要手段,。（生物谷 Bioon.com)
doi:10.1093/hmg/ddq155
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Genome-wide association study of circulating vitamin D levels
Jiyoung Ahn1,†, Kai Yu2,†, Rachael Stolzenberg-Solomon2, K. Claire Simon3, Marjorie L. McCullough6, Lisa Gallicchio7, Eric J. Jacobs6, Alberto Ascherio3,4,8, Kathy Helzlsouer7, Kevin B. Jacobs2, Qizhai Li9, Stephanie J. Weinstein2, Mark Purdue2, Jarmo Virtamo10, Ronald Horst11, William Wheeler12, Stephen Chanock2, David J. Hunter3,4,5, Richard B. Hayes1, Peter Kraft4,5 and Demetrius Albanes2
The primary circulating form of vitamin D, 25-hydroxy-vitamin D [25(OH)D], is associated with multiple medical outcomes, including rickets, osteoporosis, multiple sclerosis and cancer. In a genome-wide association study (GWAS) of 4501 persons of European ancestry drawn from five cohorts, we identified single-nucleotide polymorphisms (SNPs) in the gene encoding group-specific component (vitamin D binding) protein, GC, on chromosome 4q12-13 that were associated with 25(OH)D concentrations: rs2282679 (P = 2.0 × 10−30), in linkage disequilibrium (LD) with rs7041, a non-synonymous SNP (D432E; P = 4.1 × 10−22) and rs1155563 (P = 3.8 × 10−25). Suggestive signals for association with 25(OH)D were also observed for SNPs in or near three other genes involved in vitamin D synthesis or activation: rs3829251 on chromosome 11q13.4 in NADSYN1 [encoding nicotinamide adenine dinucleotide (NAD) synthetase; P = 8.8 × 10−7], which was in high LD with rs1790349, located in DHCR7, the gene encoding 7-dehydrocholesterol reductase that synthesizes cholesterol from 7-dehydrocholesterol; rs6599638 in the region harboring the open-reading frame 88 (C10orf88) on chromosome 10q26.13 in the vicinity of ACADSB (acyl-Coenzyme A dehydrogenase), involved in cholesterol and vitamin D synthesis (P = 3.3 × 10−7); and rs2060793 on chromosome 11p15.2 in CYP2R1 (cytochrome P450, family 2, subfamily R, polypeptide 1, encoding a key C-25 hydroxylase that converts vitamin D3 to an active vitamin D receptor ligand; P = 1.4 × 10−5). We genotyped SNPs in these four regions in 2221 additional samples and confirmed strong genome-wide significant associations with 25(OH)D through meta-analysis with the GWAS data for GC (P = 1.8 × 10−49), NADSYN1/DHCR7 (P = 3.4 × 10−9) and CYP2R1 (P = 2.9 × 10−17), but not C10orf88 (P = 2.4 × 10−5).
