The T-381C SNP in BNP gene may be modestly associated with type 2 diabetes: an updated meta-analysis in 49 279 subjects

被引：31

作者：

Choquet, Helene ^{[1
]}

Cavalcanti-Proenca, Christine ^{[1
]}

Lecoeur, Cecile ^{[1
]}

Dina, Christian ^{[1
]}

Cauchi, Stephane ^{[1
]}

Vaxillaire, Martine ^{[1
]}

Hadjadj, Samy ^{[2
]}

Horber, Fritz ^{[3
,4
]}

Potoczna, Natasha ^{[3
,4
]}

Charpentier, Guillaume ^{[5
]}

Ruiz, Juan ^{[6
]}

Hercberg, Serge ^{[7
]}

Maimaitiming, Suliya ^{[8
,9
]}

Roussel, Ronan ^{[8
,9
,10
]}

Boenhnke, Michael ^{[11
,12
]}

Jackson, Anne U. ^{[11
,12
]}

Patsch, Wolfgang ^{[13
]}

Krempler, Franz ^{[14
]}

Voight, Benjamin F. ^{[15
,16
,17
,18
]}

Altshuler, David ^{[15
,16
,17
,18
,19
,20
]}

Groop, Leif ^{[21
,22
]}

Thorleifsson, Gudmar ^{[23
]}

Steinthorsdottir, Valgerdur ^{[23
]}

Stefansson, Kari ^{[23
]}

Balkau, Beverley ^{[24
]}

Froguel, Philippe ^{[1
,25
]}

Meyre, David ^{[1
]}

机构：

[1] Inst Pasteur, Inst Biol, CNRS 8090, F-59019 Lille, France

[2] Univ Poitiers, CHU Poitiers, INSERM, CIC 0802,U927,UFR Med Pharm, Poitiers, France

[3] Dept Med, Clin Lindberg, Dept Surg & Internal Med, Winterthur, Switzerland

[4] Univ Bern, Bern, Switzerland

[5] Ctr Hosp Sud Francilien, Dept Endocrinol Diabetol, Corbeil Essonnes, France

[6] CHUV BH19, Lausanne, Switzerland

[7] Univ Paris, Cnam, INRA, INSERM,U557,U1125, Bobigny, France

[8] INSERM, U695, Paris, France

[9] Univ Paris 07, Fac Med Xavier Bichat, Paris, France

[10] Hop Xavier Bichat, AP HP, Paris, France

[11] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA

[12] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA

[13] Paracelsus Med Univ, Dept Lab Med, Salzburg, Austria

[14] Krankenhaus Hallein, Dept Internal Med, A-5400 Hallein, Austria

[15] Broad Inst Harvard, Cambridge, MA 02142 USA

[16] MIT, Cambridge, MA 02142 USA

[17] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA

[18] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA

[19] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA

[20] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA

[21] Lund Univ, Malmo Univ Hosp, Diabet & Endocrinol Res Unit, Dept Clin Sci, SE-20502 Malmo, Sweden

[22] Univ Helsinki, Helsinki Univ Hosp, Dept Med, FIN-00300 Helsinki, Finland

[23] deCODE Genet, IS-101 Reykjavik, Iceland

[24] Univ Paris Sud, INSERM, U780, IFR69, Villejuif, France

[25] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Dept Genom Med, London W12 ONN, England

来源：

HUMAN MOLECULAR GENETICS | 2009年 / 18卷 / 13期

关键词：

BRAIN NATRIURETIC PEPTIDE; GENOME-WIDE ASSOCIATION; K121Q POLYMORPHISM; COMMON VARIANTS; HEART-FAILURE; RISK; OBESITY; LOCI; SUSCEPTIBILITY; IMPACT;

D O I：

10.1093/hmg/ddp169

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A recent study reported an association between the brain natriuretic peptide (BNP) promoter T-381C polymorphism (rs198389) and protection against type 2 diabetes (T2D). As replication in several studies is mandatory to confirm genetic results, we analyzed the T-381C polymorphism in seven independent case-control cohorts and in 291 T2D-enriched pedigrees totalling 39 557 subjects of European origin. A meta-analysis of the seven case-control studies (n = 39 040) showed a nominal protective effect [odds ratio (OR) = 0.86 (0.79-0.94), P = 0.0006] of the CC genotype on T2D risk, consistent with the previous study. By combining all available data (n = 49 279), we further confirmed a modest contribution of the BNP T-381C polymorphism for protection against T2D [OR = 0.86 (0.80-0.92), P = 1.4 x 10(-5)]. Potential confounders such as gender, age, obesity status or family history were tested in 4335 T2D and 4179 normoglycemic subjects and they had no influence on T2D risk. This study provides further evidence of a modest contribution of the BNP T-381C polymorphism in protection against T2D and illustrates the difficulty of unambiguously proving modest-sized associations even with large sample sizes.

引用

页码：2495 / 2501

页数：7

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