rs693 — APOB XbaI (C/T)

Silent variant affecting LDL particle number and lipid metabolism; A allele carriers have higher ApoB, LDL-C, and total cholesterol levels

See your personal result for APOB

Upload your DNA data to find out which genotype you carry and what it means for you.

Upload your DNA data

Works with 23andMe, AncestryDNA, and other DNA test exports. Results in under 60 seconds.

APOB XbaI — The Silent Variant That Speaks Volumes for Heart Health

The rs693 variant, known historically as the XbaI polymorphism, sits in exon 26 of the APOB gene11 APOB gene
apolipoprotein B, the structural protein of LDL particles. Despite being a "silent" or synonymous mutation—the DNA change from C to T doesn't alter the amino acid (both code for threonine)—this variant has surprisingly robust effects on blood lipid levels and cardiovascular risk. It's a reminder that not all functional variants change protein sequence22 It's a reminder that not all functional variants change protein sequence
some affect mRNA stability, splicing efficiency, or are in linkage disequilibrium with truly causal variants.

The Mechanism

The rs693 SNP changes position 7673 in the APOB gene from cytosine (C) to thymine (T), creating a restriction site for the XbaI enzyme—hence its historical name. This transition occurs at codon 2488, changing ACC to ACT, but both encode threonine. Despite the synonymous nature, the A allele is consistently associated with elevated apolipoprotein B levels33 Despite the synonymous nature, the A allele is consistently associated with elevated apolipoprotein B levels
the key structural protein in LDL, VLDL, and other atherogenic particles.

The mechanism likely involves effects on mRNA stability or translation efficiency rather than direct protein structure changes. ApoB is the main protein component of LDL particles44 LDL particles
each LDL particle contains exactly one ApoB-100 molecule, making ApoB count a direct measure of atherogenic particle number. More ApoB means more LDL particles capable of infiltrating arterial walls and initiating atherosclerosis.

The Evidence

The evidence for rs693's cardiovascular impact is substantial. A 2017 meta-analysis of 61 studies including 50,018 subjects55 2017 meta-analysis of 61 studies including 50,018 subjects
showed A allele carriers had significantly higher ApoB levels (SMD 0.26), LDL-C (SMD 0.22), total cholesterol (SMD 0.24), and triglycerides (SMD 0.12). They also had slightly lower HDL-C (SMD -0.06).

A meta-analysis specific to Han Chinese populations66 meta-analysis specific to Han Chinese populations
analyzed 1,195 CHD patients and 1,178 controls, confirming the XbaI A allele confers significant CHD risk.

The A allele frequency varies dramatically by ancestry: 49-50% in Europeans, 38% in Africans and Latinos, 45% in South Asians, but only 2-10% in East Asians. This makes the variant particularly relevant for European-ancestry individuals, where roughly half the population carries at least one copy.

Practical Implications

If you're a T carrier, your baseline lipid profile is likely shifted toward higher atherogenic particle counts. This doesn't guarantee cardiovascular disease— many factors contribute to risk—but it does mean your LDL particle number may be higher than LDL-C alone would suggest. ApoB directly measures particle number77 ApoB directly measures particle number
and is increasingly recognized as superior to LDL-C for risk assessment when discordant.

Dietary response may differ by genotype. Saturated fat intake tends to raise LDL-C more in those genetically predisposed to higher ApoB production. Some evidence suggests T carriers benefit more from dietary modifications targeting particle number reduction: prioritizing monounsaturated fats, increasing soluble fiber, and limiting refined carbohydrates that drive VLDL and small dense LDL production.

Statin response can vary by APOB genotype, though rs693 itself has shown mixed results in pharmacogenetic studies. More important is ensuring treatment targets account for ApoB or non-HDL-C, not just LDL-C, if you're a T carrier—your particle number may be higher than cholesterol-based calculations suggest.

Interactions

The related rs17240441 variant (a 9-bp insertion/deletion in APOB exon 1) also affects ApoB and lipid levels, with combined effects possible when both variants are present. Additionally, variants in MTHFR (like rs1801133) can interact with lipid metabolism through homocysteine pathways, potentially compounding cardiovascular risk in those with elevated ApoB.

Dietary gene-nutrient interactions are relevant: the effect of rs693 on lipid levels may be modified by saturated fat intake, omega-3 consumption, and overall dietary pattern. Some studies suggest Mediterranean-style diets may attenuate the lipid-raising effects of the A allele more effectively than high-saturated-fat Western diets.

Genotype Interpretations

What each possible genotype means for this variant.

GG Low ApoB Baseline Normal

Typical apolipoprotein B production and LDL particle metabolism

You have two copies of the G allele, the more common form in most populations (except Europeans). This genotype is associated with lower baseline apolipoprotein B and LDL particle counts. About 28% of people of European descent have this genotype, though it's more common in East Asian populations (around 80-90%).

AG Intermediate ApoB Intermediate

Moderately elevated apolipoprotein B and LDL particle numbers compared to GG genotype

You have one copy of the A allele, which is associated with moderately elevated apolipoprotein B, LDL cholesterol, and total cholesterol levels. About 48% of people of European descent share this genotype. The effect is intermediate between CC and AA genotypes.

AA High ApoB Production High

Significantly elevated apolipoprotein B and LDL particle numbers compared to CC/GA genotypes

You have two copies of the A allele, associated with the highest apolipoprotein B, LDL cholesterol, total cholesterol, and triglyceride levels among the three genotypes. About 24% of people of European descent share this genotype.