Seven Lipoprotein Lipase Gene Polymorphisms, Lipid Fractions, and Coronary Disease: A HuGE Association Review and Meta-Analysis

Abstract

Lipoprotein lipase (LPL) is a key enzyme in lipoprotein metabolism and a major candidate gene for coronary heart disease (CHD). The authors assessed associations between 7 LPL polymorphisms and lipid fractions and CHD risk in population-based cohort, case-control, and cross-sectional studies published by January 2007. Meta-analyses of 22,734 CHD cases and 50,177 controls in 89 association studies focused on the relations of the T-93G (rs1800590), D9N (rs1801177), G188E, N291S (rs268), PvuII (rs285), HindIII (rs320), and S447X (rs328) polymorphisms to high density lipoprotein cholesterol, triglycerides, myocardial infarction, or coronary stenosis. Carriers of 9N or 291S had modestly adverse lipid profiles. Carriers of the less common allele of HindIII or of 447X had modestly advantageous profiles. The combined odds ratio for CHD among carriers was 1.33 (95% confidence interval (CI): 1.14, 1.56) for 9N, 1.07 (95% CI: 0.96, 1.20) for 291S, 0.89 (95% CI: 0.81, 0.98) for the less common HindIII allele, and 0.84 (95% CI: 0.75, 0.94) for 447X. For T-93G (odds ratio (OR) = 1.22, 95% CI: 0.98, 1.52) and PvuII (OR = 0.96, 95% CI: 0.89, 1.04), there were null associations with lipid levels or CHD risk; information on G188E was limited (OR = 2.80, 95% CI: 0.88, 8.87). The study of LPL genotypes confirms the existence of close interrelations between high density lipoprotein cholesterol and triglyceride pathways. The influence of these genotypes on CHD risk warrants further investigation.

Оценка Эффективности Гиполипидемической Терапии Розувастатином У Больных Ишемической Болезнью Сердца В Зависимости От Генотипов Липопротеинлипазы

“…Ïîëèìîðôèçìû ãåíà LPL îïðå-äåëÿþò ôóíêöèîíàëüíóþ àêòèâíîñòü ôåðìåíòà è, òà-êèì îáðàçîì, ìîãóò âíîñèòü âêëàä â ïðåäðàñïîëîaeåí-íîñòü íîñèòåëåé ê ãèïåðëèïèäåìèè (ÃËÏ). Îäíèì èç ÷àñòûõ ïîëèìîðôèçìîâ ãåíà LPL ÿâëÿåòñÿ çàìåíà ãóà-íèíà (G) íà òèìèí (T) â ïîëîaeåíèè + 495 èíòðîíà 8, èçìåíÿþùàÿ ñàéò óçíàâàíèÿ ðåñòðèêòàçîé Hind III, òàê íàçûâàåìûé Hind III-ïîëèìîðôèçì [3], âëèÿþùèé íà àêòèâíîñòü ôåðìåíòà [7,13]. Äàííûé ïîëèìîðôèçì àññîöèèðóåòñÿ ñ ïîíèaeåííûì ðèñêîì ðàçâèòèÿ ÈÁÑ, êàê ýòî áûëî íåîäíîêðàòíî îáíàðóaeåíî â ðåòðîñïåê-òèâíûõ èññëåäîâàíèÿõ [3,12,13].…”

“…Îñíîâíîé ïðè÷èíîé ÈÁÑ ÿâëÿåòñÿ àòåðîñêëåðîç êîðîíàðíûõ àð-òåðèé, âîçíèêàþùèé â ðåçóëüòàòå íàðóøåíèÿ îáìåíà ëèïèäîâ. Ãåíû, âîâëå÷åííûå â ðåãóëÿöèþ ëèïèäíîãî îáìåíà (ËÎ), ðàññìàòðèâàþòñÿ êàê çíà÷èìûå ãåíåòè-÷åñêèå ôàêòîðû ðèñêà ÈÁÑ [7,11]. Ñðåäè âîçìîaeíûõ ãåíîâ-êàíäèäàòîâ ïîäâåðaeåííîñòè ÈÁÑ âûäåëÿþò ãåí ëèïîïðîòåèíëèïàçû (LPL ) -ôåðìåíò, îáåñïå÷èâàþ-ùèé ãèäðîëèç òðèãëèöåðèäîâ (ÒÃ) è ïðåâðàùåíèå õî-ëåñòåðèíà ëèïîïðîòåèäîâ î÷åíü íèçêîé ïëîòíîñòè (ÕÑ ËÎÍÏ) â õîëåñòåðèí ëèïîïðîòåèäîâ íèçêîé ïëîò-íîñòè (ÕÑ ËÍÏ) [4,5].…”

“…Òåì íå ìåíåå âëèÿíèå ýòîãî âçàèìîäåéñòâèÿ îêàçàëîñü ñëàáûì â ñðàâíåíèè ñ ýôôåêòîì "íåãåíåòè÷åñêèõ" ôàêòîðîâ (ïîë, íàëè÷èå ñàõàðíîãî äèàáåòà â àíàìíåçå). Âî-âòîðûõ, èçó÷àëèñü ñòàòèíû ïåðâûõ ïîêîëåíèé, òàêèå êàê ñèìâàñòàòèí, ïðàâàñòàòèí, àòîðâàñòàòèí [5,7]. Öåëüþ íàñòîÿùåãî èññëåäîâàíèÿ áûëî èçó÷åíèå âëèÿíèÿ ïîëèìîðôèçìà ãåíà LPL íà ýôôåêòèâíîñòü ãèïîëèïèäåìè÷åñêîé òåðà- …”

Dyslipidemia: Genetics and Role in the Metabolic Syndrome

“…More than 100 mutations in LPL have been identified (Murthy et al, 1996); however, only a few common nonsynonymous SNPs have been consistently associated with TG levels including rs1801177, rs328 and rs268 (Mailly et al, 1995;Rip et al, 2006;Sagoo et al, 2008;Teslovich et al, 2010;Willer et al, 2008). Two SNPs, rs1801177 and rs328, have also been consistently associated with CHD; however, there is fairly strong LD between these SNPs, at least in Caucasians (Sagoo et al, 2008).…”

“…More than 100 mutations in LPL have been identified (Murthy et al, 1996); however, only a few common nonsynonymous SNPs have been consistently associated with TG levels including rs1801177, rs328 and rs268 (Mailly et al, 1995;Rip et al, 2006;Sagoo et al, 2008;Teslovich et al, 2010;Willer et al, 2008). Two SNPs, rs1801177 and rs328, have also been consistently associated with CHD; however, there is fairly strong LD between these SNPs, at least in Caucasians (Sagoo et al, 2008). MLX interacting protein like (MLXIPL) locus encodes a transcription factor of the Myc/Max/Mad superfamily which activates, in a glucose-dependent manner, carbohydrate response element binding protein (CREBP) that is expressed in lipogenic tissues coordinating the subsequent activation of lipogenic enzymes such as fatty acid synthase (FAS) to convert dietary carbohydrate to TG (Iizuka and Horikawa, 2008).…”